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Original Article
- Association study of TYMS gene expression with TYMS and ENOSF1 genetic variants in neoadjuvant chemotherapy response of gastric cancer
- Khadijeh Arjmandi, Iman Salahshourifar, Shiva Irani, Fereshteh Ameli, Mohsen Esfandbod
- J Pathol Transl Med. 2025;59(2):105-114. Published online February 25, 2025
- DOI: https://doi.org/10.4132/jptm.2024.11.05
- 3,179 View
- 141 Download
- 1 Web of Science
- 1 Crossref
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Abstract
PDF - Background
The present research was designed to study the associations between genetic variants of TYMS and ENOSF1 genes with TYMS and ENOSF1 gene expression in neoadjuvant chemotherapy response among patients with gastric cancer. Methods: Formalin-embedded and paraffin-fixed matched tumor and normal gastric cancer tissue samples from patients who received neoadjuvant 5-fluorouracil (5-FU) treatment were obtained. DNA and RNA were extracted for all samples. A 28-bp variable number tandem repeat (VNTR) at the 5' untranslated region of TYMS gene and rs2612091 and rs2741171 variants in the ENOSF1 gene were genotyped for normal tissue samples. The real-time polymerase chain reaction method was used to study the expression of ENOSF1 and TYMS genes in both normal and tumor tissues. Data were analyzed using REST 2000 and SPSS ver. 26.0 software programs. Results: A significant association between TYMS 2R3R VNTR genotypes and 5-FU therapy was found (p = .032). The 3R3R and 2R2R genotypes were significantly associated with increased and decreased survival time, respectively (p = .003). The 3R3R genotype was significantly associated with TYMS overexpression (p < .001). Moreover, a significant association was found between the rs2612091 genotype and treatment outcome (p = .017). Conclusions: This study highlights the impact of TYMS and ENOSF1 genes as predictive indicators for survival and response to 5-FU–based neoadjuvant chemotherapy in gastric cancer patients. -
Citations
Citations to this article as recorded by
- Innovative biomaterial strategies for mitigating radiotherapy toxicity: multidimensional mechanistic interventions of nano-microscale materials and hydrogels
Yifan Liu, Fengdi Jiang, Jie Song, Huaijin Qiao, Junlong Dai, Hao Bai, Shuyu Zhang
Coordination Chemistry Reviews.2026; 549: 217313. CrossRef
- Innovative biomaterial strategies for mitigating radiotherapy toxicity: multidimensional mechanistic interventions of nano-microscale materials and hydrogels
Review
- A standardized pathology report for gastric cancer: 2nd edition
- Young Soo Park, Myeong-Cherl Kook, Baek-hui Kim, Hye Seung Lee, Dong-Wook Kang, Mi-Jin Gu, Ok Ran Shin, Younghee Choi, Wonae Lee, Hyunki Kim, In Hye Song, Kyoung-Mee Kim, Hee Sung Kim, Guhyun Kang, Do Youn Park, So-Young Jin, Joon Mee Kim, Yoon Jung Choi, Hee Kyung Chang, Soomin Ahn, Mee Soo Chang, Song-Hee Han, Yoonjin Kwak, An Na Seo, Sung Hak Lee, Mee-Yon Cho
- J Pathol Transl Med. 2023;57(1):1-27. Published online January 15, 2023
- DOI: https://doi.org/10.4132/jptm.2022.12.23
- 34,231 View
- 1,526 Download
- 22 Web of Science
- 19 Crossref
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Abstract
PDF
Supplementary Material - The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
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Citations
Citations to this article as recorded by- Spatial and Temporal Tumor Heterogeneity in Gastric Cancer: Discordance of Predictive Biomarkers
Hye Seung Lee
Journal of Gastric Cancer.2025; 25(1): 192. CrossRef - PD-L1 as a Biomarker in Gastric Cancer Immunotherapy
Yunjoo Cho, Soomin Ahn, Kyoung-Mee Kim
Journal of Gastric Cancer.2025; 25(1): 177. CrossRef - Korean Gastric Cancer Association-Led Nationwide Survey on Surgically Treated Gastric Cancers in 2023
Dong Jin Kim, Jeong Ho Song, Ji-Hyeon Park, Sojung Kim, Sin Hye Park, Cheol Min Shin, Yoonjin Kwak, Kyunghye Bang, Chung-sik Gong, Sung Eun Oh, Yoo Min Kim, Young Suk Park, Jeesun Kim, Ji Eun Jung, Mi Ran Jung, Bang Wool Eom, Ki Bum Park, Jae Hun Chung, S
Journal of Gastric Cancer.2025; 25(1): 115. CrossRef - A Comprehensive and Comparative Review of Global Gastric Cancer Treatment Guidelines: 2024 Update
Sang Soo Eom, Keun Won Ryu, Hye Sook Han, Seong-Ho Kong
Journal of Gastric Cancer.2025; 25(1): 153. CrossRef - Korea, Japan, Europe, and the United States: Why are guidelines for gastric cancer different?
Emily E. Stroobant, Seong-Ho Kong, Maria Bencivenga, Takahiro Kinoshita, Tae-Han Kim, Takeshi Sano, Giovanni de Manzoni, Han-Kwang Yang, Yuko Kitagawa, Vivian E. Strong
Gastric Cancer.2025; 28(4): 559. CrossRef - Can the Japanese guidelines for endoscopic submucosal dissection be safely applied to Korean gastric cancer patients? A multicenter retrospective study based on the Korean Gastric Cancer Association nationwide survey
Hayemin Lee, Mi Ryeong Park, Junhyun Lee
Annals of Surgical Treatment and Research.2025; 109(2): 81. CrossRef - Double optimal transport for differential gene regulatory network inference with unpaired samples
Mengyu Li, Bencong Zhu, Cheng Meng, Xiaodan Fan, Laura Cantini
Bioinformatics.2025;[Epub] CrossRef - A Randomized Controlled Trial to Evaluate the Effect of Fibrin Glue on Bleeding after Gastric Endoscopic Submucosal Dissection
Tae-Se Kim, Tae-Jun Kim, Yang Won Min, Hyuk Lee, Byung-Hoon Min, Jun Haeng Lee, Poong-Lyul Rhee, Jae J. Kim
Gut and Liver.2025; 19(5): 677. CrossRef - Diagnostic accuracy of stereomicroscopy assessment of invasion depth in ex vivo specimens of early gastric cancer
Jing Wang, Lin Chang, Dong-Feng Niu, Yan Yan, Chang-Qi Cao, Shi-Jie Li, Qi Wu
World Journal of Gastroenterology.2025;[Epub] CrossRef - SMMILe enables accurate spatial quantification in digital pathology using multiple-instance learning
Zeyu Gao, Anyu Mao, Yuxing Dong, Hannah Clayton, Jialun Wu, Jiashuai Liu, ChunBao Wang, Kai He, Tieliang Gong, Chen Li, Mireia Crispin-Ortuzar
Nature Cancer.2025; 6(12): 2025. CrossRef - Genomic and Transcriptomic Characterization of Gastric Cancer with Bone Metastasis
Sujin Oh, Soo Kyung Nam, Keun-Wook Lee, Hye Seung Lee, Yujun Park, Yoonjin Kwak, Kyu Sang Lee, Ji-Won Kim, Jin Won Kim, Minsu Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim
Cancer Research and Treatment.2024; 56(1): 219. CrossRef - Microscopic tumor mapping of post-neoadjuvant therapy pancreatic cancer specimens to predict post-surgical recurrence: A prospective cohort study
Yeshong Park, Yeon Bi Han, Jinju Kim, MeeYoung Kang, Boram Lee, Eun Sung Ahn, Saemi Han, Haeryoung Kim, Hee-Young Na, Ho-Seong Han, Yoo-Seok Yoon
Pancreatology.2024; 24(4): 562. CrossRef - Effect of Neoadjuvant Chemotherapy on Tumor-Infiltrating Lymphocytes in Resectable Gastric Cancer: Analysis from a Western Academic Center
Elliott J. Yee, Danielle Gilbert, Jeffrey Kaplan, Sachin Wani, Sunnie S. Kim, Martin D. McCarter, Camille L. Stewart
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Soomin Ahn, Yoonjin Kwak, Gui Young Kwon, Kyoung-Mee Kim, Moonsik Kim, Hyunki Kim, Young Soo Park, Hyeon Jeong Oh, Kyoungyul Lee, Sung Hak Lee, Hye Seung Lee
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Moonsik Kim, Byung Woog Kang, Jihyun Park, Jin Ho Baek, Jong Gwang Kim
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T.-Y. Kim, Y. Kwak, S.K. Nam, D. Han, D.-Y. Oh, S.-A. Im, H.S. Lee
ESMO Open.2024; 9(12): 104000. CrossRef - Pathological Interpretation of Gastric Tumors in Endoscopic Submucosal Dissection
Jung Yeon Kim
Journal of Digestive Cancer Research.2023; 11(1): 15. CrossRef - Histopathology of Gastric Cancer
Baek-hui Kim, Sung Hak Lee
The Korean Journal of Helicobacter and Upper Gastrointestinal Research.2023; 23(2): 143. CrossRef - Endoscopic submucosal dissection hands-on training with artificial mucosal layer EndoGEL
Tae-Se Kim, Jun Haeng Lee
Journal of Innovative Medical Technology.2023; 1(1): 5. CrossRef
- Spatial and Temporal Tumor Heterogeneity in Gastric Cancer: Discordance of Predictive Biomarkers
Original Articles
- Extremely well-differentiated adenocarcinoma of the stomach: diagnostic pitfalls in endoscopic biopsy
- Jongwon Lee, In-Seob Lee, Ji Yong Ahn, Young Soo Park, Jihun Kim
- J Pathol Transl Med. 2022;56(2):63-72. Published online November 16, 2021
- DOI: https://doi.org/10.4132/jptm.2021.10.12
- 8,453 View
- 470 Download
- 4 Web of Science
- 4 Crossref
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Abstract
PDFSupplementary Material
- Background
Extremely well-differentiated adenocarcinoma (EWDA) is a deceptively bland-looking adenocarcinoma of the stomach. It often causes diagnostic problems, especially in endoscopic biopsy samples. To better recognize this deceptively bland lesion, we carefully reviewed a series of EWDAs treated at our institution.
Methods
A total of 55 specimens from 19 patients were obtained. Endoscopic, gross and microscopic features defining EWDA were described and documented. For comparison, hyperplastic polyp specimens were randomly selected and analyzed.
Results
Most cases (18 of 19, 94.7%) were advanced gastric cancer (AGC) and primarily located in the body of the stomach (15 of 19, 79.0%). The majority of AGCs were non-ulcerated (11 of 18, 61.1%) with an undermining growth pattern and a relatively small mucosal involvement. Specific histologic features included an irregular glandular shape, an undulating apical cytoplasmic border, disproportionately large glands, a variably distended mucinous cytoplasm. Classical features, such as small infiltrating glands or desmoplastic reactions, were barely observed. Identification of irregularly spaced nuclei and disruption of the foveolar epithelial structure, along with atypical features described above were helpful in making a diagnosis especially in gastric forceps biopsies.
Conclusions
Awareness of the histomorphologic characteristics described in this report would lead to timely diagnosis and prevent repeated endoscopic procedures. -
Citations
Citations to this article as recorded by- Artificial intelligence-assisted diagnosis of early gastric cancer: present practice and future prospects
Changda Lei, Wenqiang Sun, Kun Wang, Ruixia Weng, Xiuji Kan, Rui Li
Annals of Medicine.2025;[Epub] CrossRef - Unusual or Uncommon Histology of Gastric Cancer
Jinho Shin, Young Soo Park
Journal of Gastric Cancer.2024; 24(1): 69. CrossRef - A case of gastric adenocarcinoma with pyloric gland-type infiltrating submucosa
Kaiho Hirata, Shusuke Yagi, Hideki Miyazaki, Kazuhiko Yamada, Naoki Akazawa, Naoki Enomoto, Kyoko Nohara, Chizu Yokoi, Toru Igari, Norihiro Kokudo
Surgical Case Reports.2024;[Epub] CrossRef - Gastric-type extremely well-differentiated adenocarcinoma of the stomach: A rare tumor with diagnostic difficulties and high inter-observer variation in endoscopic pinch biopsies
Soomin Ahn, Sujin Park, Hyun Hee Koh, Han Gyeol Kim, Hyunjin Kim, Jae Yeong Son, Boram Lee, Hyunwoo Lee, Soohyun Hwang, Junhun Cho, Yun Kyung Lee, Ryoji Kushima, Amitabh Srivastava, Kyoung-Mee Kim
Pathology - Research and Practice.2024; 263: 155599. CrossRef
- Artificial intelligence-assisted diagnosis of early gastric cancer: present practice and future prospects
- Deep learning for computer-assisted diagnosis of hereditary diffuse gastric cancer
- Sean A. Rasmussen, Thomas Arnason, Weei-Yuarn Huang
- J Pathol Transl Med. 2021;55(2):118-124. Published online January 22, 2021
- DOI: https://doi.org/10.4132/jptm.2020.12.22
- 5,229 View
- 134 Download
- 9 Web of Science
- 9 Crossref
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Abstract
PDF
- Background
Patients with hereditary diffuse gastric cancer often undergo prophylactic gastrectomy to minimize cancer risk. Because intramucosal poorly cohesive carcinomas in this setting are typically not grossly visible, many pathologists assess the entire gastrectomy specimen microscopically. With 150 or more slides per case, this is a major time burden for pathologists. This study utilizes deep learning methods to analyze digitized slides and detect regions of carcinoma.
Methods
Prophylactic gastrectomy specimens from seven patients with germline CDH1 mutations were analyzed (five for training/validation and two for testing, with a total of 133 tumor foci). All hematoxylin and eosin slides containing cancer foci were digitally scanned, and patches of size 256×256 pixels were randomly extracted from regions of cancer as well as from regions of normal background tissue, resulting in 15,851 images for training/validation and 970 images for testing. A model with DenseNet-169 architecture was trained for 150 epochs, then evaluated on images from the test set. External validation was conducted on 814 images scanned at an outside institution.
Results
On individual patches, the trained model achieved a receiver operating characteristic (ROC) area under the curve (AUC) of 0.9986. This enabled it to maintain a sensitivity of 90% with a false-positive rate of less than 0.1%. On the external validation dataset, the model achieved a similar ROC AUC of 0.9984. On whole slide images, the network detected 100% of tumor foci and correctly eliminated an average of 99.9% of the non-cancer slide area from consideration.
Conclusions
Overall, our model shows encouraging progress towards computer-assisted diagnosis of hereditary diffuse gastric cancer. -
Citations
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- Now and future of artificial intelligence-based signet ring cell diagnosis: A survey
Review
- Tumor immune response and immunotherapy in gastric cancer
- Yoonjin Kwak, An Na Seo, Hee Eun Lee, Hye Seung Lee
- J Pathol Transl Med. 2020;54(1):20-33. Published online November 1, 2019
- DOI: https://doi.org/10.4132/jptm.2019.10.08
- 17,977 View
- 748 Download
- 72 Web of Science
- 67 Crossref
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Abstract
PDF
- Remarkable developments in immuno-oncology have changed the landscape of gastric cancer (GC) treatment. Because immunotherapy intervenes with tumor immune response rather than directly targeting tumor cells, it is important to develop a greater understanding of tumor immunity. This review paper summarizes the tumor immune reaction and immune escape mechanisms while focusing on the role of T cells and their co-inhibitory signals, such as the immune checkpoint molecules programmed death-1 and programmed deathligand 1 (PD-L1). This paper also describes past clinical trials of immunotherapy for patients with GC and details their clinical implications. Strong predictive markers are essential to improve response to immunotherapy. Microsatellite instability, Epstein-Barr virus, PD-L1 expression, and tumor mutational burden are now regarded as potent predictive markers for immunotherapy in patients with GC. Novel immunotherapy and combination therapy targeting new immune checkpoint molecules such as lymphocyte-activation gene 3, T cell immunoglobulin, and mucin domain containing-3, and indoleamine 2,3-dioxygenase have been suggested, and trials are ongoing to evaluate their safety and efficacy. Immunotherapy is an important treatment option for patients with GC and has great potential for improving patient outcome, and further research in immuno-oncology should be carried out.
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Case Study
- Multiple Neuroendocrine Tumors in Stomach and Duodenum in a Multiple Endocrine Neoplasia Type 1 Patient
- Bohyun Kim, Han-Kwang Yang, Woo Ho Kim
- J Pathol Transl Med. 2018;52(2):126-129. Published online December 21, 2017
- DOI: https://doi.org/10.4132/jptm.2017.09.16
- 8,776 View
- 145 Download
- 1 Web of Science
- 1 Crossref
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Abstract
PDF
- A 67-year-old woman with a history of subtotal parathyroidectomy, distal pancreatectomy, and total splenectomy 23 years prior underwent surgical gastric resection for neuroendocrine tumors of the stomach and duodenum. Meticulous examination of the entire stomach and duodenum revealed multiple scattered, minute neuroendocrine tumors. To the best of our knowledge, this is the first case report of a patient diagnosed with gastroduodenal neuroendocrine tumors associated with multiple endocrine neoplasia type 1 (MEN 1) in whom complete histologic mapping of the whole gastrectomy specimen was performed. The presence of MEN 1–associated neuroendocrine tumors in the stomach is very rare, but should be considered in patients diagnosed with MEN 1 who present with a new tumor in the stomach.
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Citations
Citations to this article as recorded by- A Case of Asymptomatic Multiple Endocrine Neoplasia Type I with Thymic Carcinoid
Suk Ki Park, Moon Won Lee, In Sub Han, Young Joo Park, Sung Yong Han, Joon Woo Park, Bong Eun Lee, Gwang Ha Kim, Sang Soo Kim
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Original Articles
- Extramural Perineural Invasion in pT3 and pT4 Gastric Carcinomas
- Alejandro España-Ferrufino, Leonardo S. Lino-Silva, Rosa A. Salcedo-Hernández
- J Pathol Transl Med. 2018;52(2):79-84. Published online November 9, 2017
- DOI: https://doi.org/10.4132/jptm.2017.11.01
- 10,166 View
- 143 Download
- 12 Web of Science
- 12 Crossref
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Abstract
PDF
- Background
Perineural invasion (PNI) is widely studied in malignant tumors, and its prognostic significance is well demonstrated. Most studies have focused on evaluating the mural PNI (mPNI); however, extramural PNI (ePNI) may influence the prognosis in gastric cancer. We evaluated the prognostic value of ePNI compared with mPNI in gastric cancer in this observational comparative cross-sectional study.
Methods
Seventy-three pT3 and pT4 gastric carcinomas with PNI were evaluated. Forty-eight (65.7%) were in the mPNI group and the remaining in the ePNI group.
Results
Clinicopathologic characteristics between the two groups were similar, except for the outcomes. The 5-year disease-specific survival (DSS) rate was 64% for the mPNI group and 50% for the ePNI group (p=.039), a difference that did not remain significant in multivariate analysis. The only independent adverse prognostic factor in multivariate analysis was the presence of lymph node metastasis (hazard ratio, 1.757; 95% confidence interval, 1.082 to 2.854; p=.023).
Conclusions
We demonstrated the prognostic effect of ePNI for DSS in surgically resected pT3–pT4 gastric cancer patients. ePNI could be considered in the staging and prognostic systems of gastric cancer to stratify patients with a high risk of recurrence. -
Citations
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Didem Karakaş
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Mariana-Tomás de Carvalho, Margarida Henriques-Pereira, Maria V. Monteiro, Meriem Lamghari, João F. Mano, Vítor M. Gaspar
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Ruochen Cong, Jialei Ming, Ruonan Xu, Liyu Zhu, Xinyue Wang, Zhengqi Zhu
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- HER2 Status and Its Heterogeneity in Gastric Carcinoma of Vietnamese Patient
- Dang Anh Thu Phan, Vu Thien Nguyen, Thi Ngoc Ha Hua, Quoc Dat Ngo, Thi Phuong Thao Doan, Sao Trung Nguyen, Anh Tu Thai, Van Thanh Nguyen
- J Pathol Transl Med. 2017;51(4):396-402. Published online June 19, 2017
- DOI: https://doi.org/10.4132/jptm.2017.04.24
- 11,414 View
- 163 Download
- 10 Web of Science
- 9 Crossref
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Abstract
PDF
- Background
Human epidermal growth factor receptor 2 (HER2) is related to the pathogenesis and poor outcome of numerous types of carcinomas, including gastric carcinoma. Gastric cancer patients with HER2 positivity have become potential candidates for targeted therapy with trastuzumab.
Methods
We investigated 208 gastric cancer specimens using immunohistochemistry (IHC), fluorescence in situ hybridization and dual in situ hybridization (ISH). We also investigated the concordance between IHC and ISH. The correlation between HER2 status and various clinicopathological findings was also investigated.
Results
In total, 15.9% (33/208) and 24.5% (51/208) of gastric cancers showed HER2 gene amplification and protein overexpression, respectively. A high level of concordance between ISH and IHC analyses (91.3%, κ = 0.76) was found. A significant correlation between HER2 status and intestinal-type (p < .05) and differentiated carcinomas (p < .05) was also noted. The HER2 heterogeneity was high in gastric cancers; we found 68.8% phenotypic heterogeneity and 57.6% genotypic heterogeneity. Heterogeneity in HER2 protein expression and gene amplification showed a close association with diffuse histologic type and IHC 2+.
Conclusions
HER2 protein overexpression and gene amplification were detected in 24.5% and 15.9% of gastric cancer specimens, respectively. Intestinal-type showed a higher level of HER2 protein overexpression and gene amplification than diffuse type. HER2 status also showed a significant relationship with well- and moderately-differentiated carcinomas. The ratio of phenotypic and genotypic heterogeneity of HER2 was high in gastric carcinomas and was associated with HER2 IHC 2+ and diffuse histologic type. -
Citations
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Steven Wanda, Gorretti Nassali, Brian Bbosa, Francis Basimbe, Joviah Akulu, Davis Nsamba, Praise Nimusiima, Joshua Muhumuza, Emmanuel Othieno, Maxwel Dancan Okuku
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Case Study
- Perivascular Epithelioid Cell Tumor in the Stomach
- Sun Ah Shin, Jiwoon Choi, Kyung Chul Moon, Woo Ho Kim
- J Pathol Transl Med. 2017;51(4):428-432. Published online April 4, 2017
- DOI: https://doi.org/10.4132/jptm.2016.09.16
- 9,773 View
- 141 Download
- 6 Web of Science
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Abstract
PDF
- Perivascular epithelioid cell tumors or PEComas can arise in any location in the body. However, a limited number of cases of gastric PEComa have been reported. We present two cases of gastric PEComas. The first case involved a 62-year-old woman who presented with a 4.2 cm gastric subepithelial mass in the prepyloric antrum, and the second case involved a 67-year-old man with a 5.0 cm mass slightly below the gastroesophageal junction. Microscopic examination revealed that both tumors were composed of perivascular epithelioid cells that were immunoreactive for melanocytic and smooth muscle markers. Prior to surgery, the clinical impression of both tumors was gastrointestinal stromal tumor (GIST), and the second case was erroneously diagnosed as GIST even after microscopic examination. Although gastric PEComa is a very rare neoplasm, it should be considered in the differential diagnosis of gastric submucosal lesions.
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Review
- Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives
- Yoon Young Choi, Sung Hoon Noh, Jae-Ho Cheong
- J Pathol Transl Med. 2016;50(1):1-9. Published online October 26, 2015
- DOI: https://doi.org/10.4132/jptm.2015.09.10
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Abstract
PDF
- Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus–positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.
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Jiwon Koh, Hee Eun Lee, Woo Ho Kim, Hye Seung Lee, Ju-Seog Lee
PLOS ONE.2017; 12(3): e0174814. CrossRef - Perioperative chemotherapy for resectable gastric cancer – what is the evidence?
Erling A Bringeland, Hans H Wasmuth, Jon E Grønbech
Scandinavian Journal of Gastroenterology.2017; 52(6-7): 647. CrossRef - Molecular classifications of gastric cancers: Novel insights and possible future applications
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World Journal of Gastrointestinal Oncology.2017; 9(5): 194. CrossRef - GRAM domain-containing protein 1B (GRAMD1B), a novel component of the JAK/STAT signaling pathway, functions in gastric carcinogenesis
Puja Khanna, Pei Jou Chua, Belinda Shu Ee Wong, Changhong Yin, Aye Aye Thike, Wei Keat Wan, Puay Hoon Tan, Gyeong Hun Baeg
Oncotarget.2017; 8(70): 115370. CrossRef - Clinicopathologic implications of immune classification by PD-L1 expression and CD8-positive tumor-infiltrating lymphocytes in stage II and III gastric cancer patients
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Oncotarget.2017; 8(16): 26356. CrossRef
- Establishment and characterization of a new mouse gastric carcinoma cell line, MCC
Case Study
- Gastric-Type Extremely Well-Differentiated Adenocarcinoma of the Stomach: A Challenge for Preoperative Diagnosis
- Mee Joo, Song Hee Han
- J Pathol Transl Med. 2016;50(1):71-74. Published online September 30, 2015
- DOI: https://doi.org/10.4132/jptm.2015.07.14
- 13,501 View
- 179 Download
- 10 Web of Science
- 10 Crossref
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Abstract
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- Gastric-type extremely well-differentiated adenocarcinoma (EWDA) is a rare type of gastric adenocarcinoma characterized by infiltration of well-formed mucinous glands with little or no nuclear atypia, which resemble foveolar epithelium or pyloric glands. Because of its high degree of differentiation, preoperative biopsy diagnosis of gastric-type EWDA is very difficult. We encountered a case of gastric-type EWDA, manifesting as a Borrmann type 4 lesion, in a 47-year-old man. Despite four repeated biopsies, the preoperative biopsy diagnosis was not conclusive due to the scarcity of diagnostic tumor cells and lack of knowledge regarding the unusual histologic findings of gastric-type EWDA. We herein describe the histologic findings of gastric-type EWDA in detail, with the aim of facilitating a preoperative biopsy diagnosis and understanding of this rare type of gastric adenocarcinoma.
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Jinho Shin, Young Soo Park
Journal of Gastric Cancer.2024; 24(1): 69. CrossRef - Clinical pathological characteristics of “crawling-type” gastric adenocarcinoma cancer: A case report
Yong-Wei Xu, Yan Song, Jun Tian, Ba-Cui Zhang, Yu-Sheng Yang, Jing Wang
World Journal of Gastrointestinal Oncology.2024; 16(4): 1660. CrossRef - Gastric-type extremely well-differentiated adenocarcinoma of the stomach: A rare tumor with diagnostic difficulties and high inter-observer variation in endoscopic pinch biopsies
Soomin Ahn, Sujin Park, Hyun Hee Koh, Han Gyeol Kim, Hyunjin Kim, Jae Yeong Son, Boram Lee, Hyunwoo Lee, Soohyun Hwang, Junhun Cho, Yun Kyung Lee, Ryoji Kushima, Amitabh Srivastava, Kyoung-Mee Kim
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Sun-Young Lee
The Korean Journal of Helicobacter and Upper Gastrointestinal Research.2021; 21(1): 10. CrossRef - Preoperative diagnosis of a gastric extremely well-differentiated adenocarcinoma
Katsushi Suenaga, Shiro Matsumoto, Alan Kawarai Lefor, Yoshimasa Miura, Yoshinori Hosoya, Daigo Kuboki, Hidenori Haruta, Kentaro Kurashina, Atsushi Kihara, Daisuke Matsubara, Yasunari Sakuma, Joji Kitayama, Naohiro Sata
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Chengfang Li, Xinglong Wu, Shuang Yang, Xiaorong Yang, Jin Yao, Hong Zheng
Diagnostic Pathology.2020;[Epub] CrossRef - Gastric Adenocarcinoma of the Fundic Gland Type
Mark A Benedict, Gregory Y Lauwers, Dhanpat Jain
American Journal of Clinical Pathology.2018; 149(6): 461. CrossRef
- Unusual or Uncommon Histology of Gastric Cancer
Original Article
- Endogenous Gastric-Resident Mesenchymal Stem Cells Contribute to Formation of Cancer Stroma and Progression of Gastric Cancer
- Eun-Kyung Kim, Hye-Jung Kim, Young-Il Yang, Jong Tae Kim, Min-Young Choi, Chang Soo Choi, Kwang-Hee Kim, Jeong-Han Lee, Won-Hee Jang, Soon-Ho Cheong
- Korean J Pathol. 2013;47(6):507-518. Published online December 24, 2013
- DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.507
- 10,217 View
- 53 Download
- 17 Crossref
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Abstract
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Background Carcinoma-associated fibroblasts (CAFs) contribute to carcinogenesis and cancer progression, although their origin and role remain unclear. We recently identified and investigated the
in situ identity and implications of gastric submucosa-resident mesenchymal stem cells (GS-MSCs) in the progression of gastric carcinogenesis.Methods We isolated GS-MSCs from gastric submucosa using hydrogel-supported organ culture and defined their identity. Isolated cells were assessed
in vitro by immunophenotype and mesengenic multipotency. Reciprocal interactions between GS-MSCs and gastric cancer cells were evaluated. To determine the role of GS-MSCs, xenografts were constructed of gastric cancer cells admixed with or without GS-MSCs.Results Isolated cells fulfilled MSCs requirements in regard to plastic adherence, stromal cell immunophenotype, and multipotency. We demonstrated a paracrine loop that gastric cancer cells enhanced the migration, proliferation, and differentiation of GS-MSCs; additionally, GS-MSCs promoted the proliferation of gastric cancer cell
in vitro . Xenograft experiments showed that GS-MSCs significantly promoted cancer growth and angiogenesis. GS-MSCs that integrated into gastric cancer became not only CAFs but also rarely endothelial cells which contributed to the formation of cellular and vascular cancer stroma.Conclusions Endogenous GS-MSCs play an important role in gastric cancer progression.
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Peiyuan Li, Huan Zhang, Tao Chen, Yajing Zhou, Jiaoyang Yang, Jin Zhou
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Case Report
- Gastric Adenocarcinoma of Fundic Gland Type: Report of Three Cases
- Eun Su Park, Young Eun Kim, Cheol Keun Park, Takashi Yao, Ryoji Kushima, Kyoung-Mee Kim
- Korean J Pathol. 2012;46(3):287-291. Published online June 22, 2012
- DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.287
- 12,343 View
- 111 Download
- 25 Crossref
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Abstract
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Recently, fundic gland type gastric adenocarcinoma (GA-FG) has been reported as a new entity. This report describes GA-FG among Koreans for the first time. From March 2008 to July 2010 we identified only three cases of GA-FG out of over 6,000 GAs resected by endoscopy or surgery. Cell differentiation by mucin proteins, pepsinogen-I, and H+/K+-ATPase was evaluated. All three cases were male patients and diagnosed as early stage GA. Histologically, GA-FGs were well-differentiated adenocarcinoma with pale gray-blue, basophilic columnar or cuboidal cells and mildly enlarged nuclei, resembling chief cells. All three cases were positive for pepsinogen-I and were classified as gastric mucin phenotype. Among three histologic subtypes of GA-FG, since tumors were mainly composed of chief cells, our three cases were classified as chief cell predominant type. In conclusion, GA-FG is very rare among Koreans and pepsinogen-I and MUC6 expression are typical immunohistochemical findings in GA-FG suggesting differentiation toward fundic glands.
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Rajkumar Vajpeyi, Jyoti Dekate
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Original Articles
- Genetic Analysis of Epstein-Barr Virus Latent Membrane Protein 1 and Immunohistochemical Expression of Transforming Growth Factor (TGF)-beta1, TGF-betaRII, p21, p16, E2F1, Thymidylate Synthase, and NF-kappaB in Epstein-Barr Virus Encoded RNA-positive Gastric Adenocarcinoma
- Mee Yon Cho, Minseob Eom, Kwang Hwa Park, Mee Dong Kim, Seung Hoon Sung, Myoung Soo Kim, Dae Sung Kim, Sun Ju Choi
- Korean J Pathol. 2006;40(3):176-184.
- 2,099 View
- 22 Download
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Abstract
PDF
- BACKGROUND
:Although clinicopathologic differences have been described between Epstein-Barr virus (EBV)-positive and negative gastric adenocarcinomas, the pathogenetic basis for these differences remains unclear. In this study, efforts were made to confirm that expression of EBV-latent membrane protein (LMP1) and immunohistochemical characteristics of EBVpositive gastric adenocarcinomas.
METHODS
We investigated genomic deletion, and RNA & protein expression of the EBV-LMP1, as well as immunohistochemical protein expression of transforming growth factor (TGF)-beta1, TGF-bata RII, p21, p16, E2F1, thymidylate synthase, and NF-kappaB in relation to EBV positive gastric adenocarcinoma.
RESULTS
A total of 38 Epstein-Barr Virus Encoded RNA-positive and 80 negative gastric carcinomas were examined. A 30 bp DNA deletion in the EBV-LMP1 gene, initiating at codon 342, was detected in 94.4% of EBVpositive cases. By RT-PCR and western blotting, EBV-LMP1 mRNA and protein expressions were absent in all cases, re-gardless of DNA deletion. No significant differences in TGF-bata1, TGF-betaRII, p21, NF-kappaB, E2F1, or thymidylate synthase expression were identified. However, the decreased expression of p16 was found in 84.2% of EBV-positive carcinomas, relative to only 57.5% of EBV-negative tumors (p=0.024).
CONCLUSION
EBV-LMP1 DNA deletion, mRNA and protein losses are highly prevalent in EBV-positive gastric adenocarcinoma among Korean patients, along with decreased p16 expression.
- Molecular Biological Characteristics of Differentiated Early Gastric Cancer on the Basis of Mucin Expression.
- Nari Shin, Hye Yeon Kim, Woo Kyung Kim, Min Gyung Park, Kyung Bin Kim, Dong Hoon Shin, Kyung Un Choi, Jee Yeon Kim, Chang Hun Lee, Gi Young Huh, Mee Young Sol, Do Youn Park
- Korean J Pathol. 2011;45(1):69-78.
- DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.69
- 4,703 View
- 23 Download
- 2 Crossref
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Abstract
PDF
- BACKGROUND
It is clear that the biologic characteristics of gastric cancer are different on the basis of mucin phenotypes. However, there are unabated controversies on the exact biologic differences of mucin expression in gastric cancer.
METHODS
We analyzed various protein expressions and microsatellite instability (MSI) status based on mucin expression in 130 differentiated early gastric adenocarcinoma cases. Furthermore, we evaluated the genomic alternation in 10 selected differentiated early gastric adenocarcinoma cases using array based comparative genomic hybridization (aCGH).
RESULTS
Intestinal mucin predominant subtype showed significantly elevated p53 protein and caudal-related homeobox 2 expression, and delocalization of beta catenin expressions compared to the gastric mucin predominant subtype. On MSI status, the gastric mucin predominant subtype more frequently showed unstable status than the intestinal mucin predominant subtype. CGH study showed more frequent chromosomal gain and loss in the intestinal mucin predominant subtype than the gastric mucin predominant subtype, albeit without statistical significance. Interestingly, there were significant differences in chromosomal alternation between four mucin phenotypes.
CONCLUSIONS
Study results suggest possible different points of biologic behaviors in early differentiated gastric adenocarcinomas by mucin expression type. -
Citations
Citations to this article as recorded by- Mucin Expression in Gastric Cancer: Reappraisal of Its Clinicopathologic and Prognostic Significance
Dae Hwan Kim, Nari Shin, Gwang Ha Kim, Geum Am Song, Tae-Yong Jeon, Dong-Heon Kim, Gregory Y. Lauwers, Do Youn Park
Archives of Pathology & Laboratory Medicine.2013; 137(8): 1047. CrossRef - Microsatellite Instability Status in Gastric Cancer: A Reappraisal of Its Clinical Significance and Relationship with Mucin Phenotypes
Joo-Yeun Kim, Na Ri Shin, Ahrong Kim, Hyun-Jeong Lee, Won-young Park, Jee-Yeon Kim, Chang-Hun Lee, Gi-Young Huh, Do Youn Park
Korean Journal of Pathology.2013; 47(1): 28. CrossRef
- Mucin Expression in Gastric Cancer: Reappraisal of Its Clinicopathologic and Prognostic Significance
- HER2 Status in Gastric Adenocarcinomas Assessed by Immunohistochemistry, Automated Silver-Enhanced In Situ Hybridization and Fluorescence In Situ Hybridization.
- Aeri Kim, Jung Min Bae, Se Won Kim, Mi Jin Gu, Young Kyung Bae
- Korean J Pathol. 2010;44(5):493-501.
- DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.493
- 4,749 View
- 35 Download
- 3 Crossref
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Abstract
PDF
- BACKGROUND
Recently, many studies have focused on human epidermal growth factor receptor 2 (HER2) status in gastric cancer due to HER2-targeted therapy using trastuzumab. We investigated HER2 overexpression and amplification and their concordance rate in Korean gastric adenocarcinomas.
METHODS
Tissue microarrays were constructed with 232 gastric adenocarcinoma samples. We performed immunohistochemistry (IHC), silver-enhanced in situ hybridization (SISH) and fluorescence in situ hybridization (FISH) for HER2.
RESULTS
IHC was negative in 94.8% (218/232), equivocal in 1.7% (4/232) and positive in 3.5% (8/232) of cases. HER2 protein expression was heterogeneous in 75% (9/12) of IHC 2+/3+ cancers. Gene amplification was observed in 6.5% (15/230) by SISH and the same 15 cases were also FISH-positive. We observed HER2 amplification in 1.4%, 27.3%, 25%, and 100% of IHC 0, 1+, 2+, and 3+ gastric adenocarcinomas, respectively. The concordance rate between IHC and SISH results was 95.7%.
CONCLUSIONS
HER2 overexpression and amplification were less frequent in gastric adenocarcinomas than breast carcinomas. Compared to breast carcinoma, (1) there may be IHC-negative but gene amplification-positive cases for HER2 and (2) frequent intratumoral heterogeneity of IHC for HER2 in gastric adenocarcinomas. -
Citations
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Kyung Won Seo, Taeyong Jeon, Sewon Kim, Sung Soo Kim, Kwanghee Kim, Byoung-Jo Suh, Sunhwi Hwang, SeongHee Choi, Seungwan Ryu, Jae Seok Min, Young-Joon Lee, Ye Seob Jee, Hyeondong Chae, Doo Hyun Yang, Sang Ho Lee
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Jun Haeng Lee, Jae G. Kim, Hye-Kyung Jung, Jung Hoon Kim, Woo Kyoung Jeong, Tae Joo Jeon, Joon Mee Kim, Young Il Kim, Keun Won Ryu, Seong-Ho Kong, Hyoung Il Kim, Hwoon-Yong Jung, Yong Sik Kim, Dae Young Zang, Jae Yong Cho, Joon Oh Park, Do Hoon Lim, Eun S
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Jun Haeng Lee, Jae G. Kim, Hye-Kyung Jung, Jung Hoon Kim, Woo Kyoung Jeong, Tae Joo Jeon, Joon Mee Kim, Young Il Kim, Keun Won Ryu, Seong-Ho Kong, Hyoung-Il Kim, Hwoon-Yong Jung, Yong Sik Kim, Dae Young Zang, Jae Yong Cho, Joon Oh Park, Do Hoon Lim, Eun S
Journal of Gastric Cancer.2014; 14(2): 87. CrossRef
- Epidemiologic Study of Human Epidermal Growth Factor Receptor 2 Expression in Advanced/Metastatic Gastric Cancer: an Assessment of Human Epidermal Growth Factor Receptor 2 Status in Tumor Tissue Samples of Gastric and Gastro-Esophageal Junction Cancer
- Detection of JC Virus T-Ag in Early Gastric Cancer.
- Eun Jeong Jang, Jung Sik Jang, Jae Hoon Kim, Han Ik Bae, In Soo Suh
- Korean J Pathol. 2010;44(5):456-461.
- DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.456
- 4,119 View
- 41 Download
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Abstract
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- BACKGROUND
JC virus (JCV) is a polyomavirus that commonly infects humans and can cause progressive multifocal leukoencephalopathy in immunocompromised patients. Recently, many reports have documented detection of JCV in gastrointestinal tract cancers. We investigated the presence of JCV in gastric adenocarcinoma, adenoma, and non-neoplastic gastric mucosa.
METHODS
We selected paraffin-embedded tissue from endoscopic mucosal resections performed from January 2007 to September 2008. DNA was extracted from the paraffin-embedded specimens of 30 adenocarcinomas, 20 adenomas of the stomach, and 20 non-neoplastic gastric mucosa. Polymerase chain reaction amplifications were performed using gene-specific primers to detect the JCV gene sequences, and immunohistochemical staining was performed to detect the T-antigen (T-Ag) protein.
RESULTS
The T-Ag sequence was detected in nine of 30 gastric cancers (30%), two of 20 adenomas (10%), and eight of 20 non-neoplastic gastric mucosa specimens (40%). T-Ag protein expression was found in five of 30 gastric cancers (16.7%) and one of 20 non-neoplastic gastric mucosa specimens (5%), whereas no expression was observed in any of the adenomas.
CONCLUSIONS
Although we could not detect a correlation between JCV and gastric cancer, we demonstrated the presence of JCV T-Ag expression in human gastric cancers. These findings suggest a possible role for JCV in gastric carcinogenesis. -
Citations
Citations to this article as recorded by- Associations Between Gastric Cancer Risk and Virus Infection Other Than Epstein-Barr Virus: A Systematic Review and Meta-analysis Based on Epidemiological Studies
Hui Wang, Xiao-Long Chen, Kai Liu, Dan Bai, Wei-Han Zhang, Xin-Zu Chen, Jian-Kun Hu
Clinical and Translational Gastroenterology.2020; 11(7): e00201. CrossRef
- Associations Between Gastric Cancer Risk and Virus Infection Other Than Epstein-Barr Virus: A Systematic Review and Meta-analysis Based on Epidemiological Studies
Case Report
- Fine Needle Aspiration Cytology of Gastric Glomus Tumor: A Case Report.
- Dong Geun Lee, Kyu Yun Jang, Myoung Ja Chung, Woo Sung Moon, Myoung Jae Kang, Ho Sung Park
- Korean J Pathol. 2010;44(4):448-452.
- DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.448
- 4,181 View
- 49 Download
- 2 Crossref
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Abstract
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- Glomus tumors of the stomach are rare and are usually found as a solitary, intramural lesion. Here, we report a case of a gastric glomus tumor in a 60-year-old woman diagnosed by endoscopic ultrasound-guided fine-needle aspiration cytology. Endoscopic ultrasound revealed a 4 x 3 cm-sized, round, isoechoic mass at the fourth layer of the gastric wall. Smears revealed cohesive clusters of small, uniform, round to polygonal cells with scant cytoplasm and round, hyperchromatic nuclei with homogeneous chromatin. Immunocytochemistry by liquid-based cytology was positive for smooth muscle actin. The cytologic diagnosis of a glomus tumor was confirmed by a specimen from the laparoscopic resection. Although the cytologic features of glomus tumors are quite distinctive, an immunocytochemical stain from a liquid-based cytology preparation can further help to ascertain the diagnosis.
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Citations
Citations to this article as recorded by- Glomus Tumor of the Stomach: A Systematic Review and Illustrative Case Report
Andrea Pansa, Laura Samà, Laura Ruspi, Federico Sicoli, Ferdinando Carlo Maria Cananzi, Vittorio Quagliuolo
Digestive Diseases.2023; 41(1): 17. CrossRef - Cytologic analysis of a glomus tumor in the left second toe: Case report
Jay Hwang, Susan McDowell, Bradley Cole, Aaron Huber, Maria Cecilia D. Reyes
Diagnostic Cytopathology.2022;[Epub] CrossRef
- Glomus Tumor of the Stomach: A Systematic Review and Illustrative Case Report
Original Articles
- Mutation and Expression of DNA2 Gene in Gastric and Colorectal Carcinomas.
- Sung Hak Lee, Yoo Ri Kim, Nam Jin Yoo, Sug Hyung Lee
- Korean J Pathol. 2010;44(4):354-359.
- DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.354
- 4,801 View
- 35 Download
- 3 Crossref
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Abstract
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- BACKGROUND
Deregulation of DNA repair and replication are involved in cancer development. DNA2 is a nuclease/helicase that plays roles in DNA repair and replication. The aim of this study was to explore DNA2 mutation and DNA2 protein expression in gastric cancers (GCs) and colorectal cancers (CRCs).
METHODS
We analyzed two mononucleotide repeats in DNA2 in 27 GCs with high microsatellite instability (MSI-H), 34 GCs with stable MSI (MSS), 29 CRCs with MSI-H and 35 CRCs with MSS by single-strand conformation polymorphism. We also analyzed DNA2 expression in GCs and CRCs either with MSI-H or MSS.
RESULTS
We found DNA2 mutations in two GCs (7.1%) and two CRCs with MSI-H (6.9%), but not in cancers with MSS. The mutations consisted of three cases of a c.2593delT and one of a c.2592_2593delTT, which would result in premature stopping of amino acid synthesis (p.Ser865Hisfsx6 and p.Ser865Thrfsx20, respectively). DNA2 expression was observed in 16 (80%) of the GCs and 15 (75%) of the CRCs with MSI-H, but all of the cancers with DNA2 frameshift mutations were weak or negative for DNA2.
CONCLUSIONS
Our data indicate that DNA2 mutation and loss of DNA2 expression occur in GCs and CRCs, and suggest that these alterations may contribute to cancer pathogenesis by deregulating DNA repair and replication. -
Citations
Citations to this article as recorded by- Multiple roles of DNA2 nuclease/helicase in DNA metabolism, genome stability and human diseases
Li Zheng, Yuan Meng, Judith L Campbell, Binghui Shen
Nucleic Acids Research.2020; 48(1): 16. CrossRef - Integration of multiple networks and pathways identifies cancer driver genes in pan-cancer analysis
Claudia Cava, Gloria Bertoli, Antonio Colaprico, Catharina Olsen, Gianluca Bontempi, Isabella Castiglioni
BMC Genomics.2018;[Epub] CrossRef - Replication intermediates that escape Dna2 activity are processed by Holliday junction resolvase Yen1
Gizem Ölmezer, Maryna Levikova, Dominique Klein, Benoît Falquet, Gabriele Alessandro Fontana, Petr Cejka, Ulrich Rass
Nature Communications.2016;[Epub] CrossRef
- Multiple roles of DNA2 nuclease/helicase in DNA metabolism, genome stability and human diseases
- Prognostic Value of Phosphorylated Akt and Survivin Expression in Gastric Adenocarcinoma.
- Soong Lee, Yun Cheol Kim, Hyeon Min Lee, Ki Sang Lee, Byung Chul Shin, Hyung Seok Kim, Jae Hyuk Lee, Chang Soo Park, Kyung Hwa Lee
- Korean J Pathol. 2010;44(3):252-258.
- DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.252
- 4,710 View
- 22 Download
- 3 Crossref
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Abstract
PDF
- BACKGROUND
pAkt (the phosphorylated form of the proto-oncogene protein c-akt) and survivin (human BIRC5 protein) are candidate apoptosis-related molecules that may be responsible for cancer progression. The aim of this study was to determine the expression of pAkt and survivin in malignant stomach neoplasm, and their value as prognostic indicators of cancer.
METHODS
The expression of pAkt and survivin in 144 cases of gastric cancer was detected by immunohistochemistry and compared with established clinicopathological parameters and prognosis of this disease.
RESULTS
Expression of pAkt showed significant correlations with depth of invasion, lymph node and distant metastasis, as well as the stage (p < 0.05 for all three correlations), but not with the Lauren classification. Survivin expression closely correlated with histological type, Lauren classification, depth of invasion, metastasis, and stage (p < 0.05 for all). The overall survival of patients with pAkt/survivin expression was inferior to that of patients with loss of pAkt/survivin expression. Cox multivariate analysis demonstrated a significant correlation between stage (p = 0.04), survivin expression (p = 0.02), and prognosis.
CONCLUSIONS
Patients with pAkt/survivin expression in gastric cancer are at increased risk of cancer-related mortality via the apoptosis resistance pathway. Expression of pAkt and survivin could be used as a prognostic indicator for gastric cancer. -
Citations
Citations to this article as recorded by- Transcriptome analysis reveals GPNMB as a potential therapeutic target for gastric cancer
Feifei Ren, Qitai Zhao, Bin Liu, Xiangdong Sun, Youcai Tang, Huang Huang, Lu Mei, Yong Yu, Hui Mo, Haibin Dong, Pengyuan Zheng, Yang Mi
Journal of Cellular Physiology.2020; 235(3): 2738. CrossRef - The Relationship Between Estrogen/Progesterone Receptor and Expression of mTOR/pAkt Proteins and the Analysis of Prognosis in Breast Cancer
Sun Wook Han, Moon Soo Lee, Sung Yong Kim, Gil Ho Kang, Zi Sun Kim, Cheol Wan Lim, Ji Hyun Lee, Hyun Ju Lee, Mee-Hye Oh, Min Hyuk Lee
Journal of Breast Disease.2013; 1(1): 8. CrossRef - Clinicopathological correlations of mTOR and pAkt expression in non-small cell lung cancer
Mee-Hye Oh, Hyun Ju Lee, Seol Bong Yoo, Xianhua Xu, Jae Sung Choi, Yong Hoon Kim, Seok Yeol Lee, Choon-Taek Lee, Sanghoon Jheon, Jin-Haeng Chung
Virchows Archiv.2012; 460(6): 601. CrossRef
- Transcriptome analysis reveals GPNMB as a potential therapeutic target for gastric cancer
- The Prognostic Significance of the Tumor-Infiltrating FoxP3-Positive Regulatory T Cells in Gastric Carcinoma.
- Sang Jae Noh, Shin Young Park, Kyung Ryoul Kim, Chan Young Kim, Keun Sang Kwon, Ho Sung Park, Ho Lee, Myoung Ja Chung, Woo Sung Moon, Kyu Yun Jang
- Korean J Pathol. 2010;44(1):9-15.
- DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.9
- 4,445 View
- 42 Download
- 2 Crossref
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Abstract
PDF
- BACKGROUND
Regulatory T cells (Tregs) are known to be key regulators of immune responses in patients with autoimmune disease and infection and also for attenuating antitumor immunity by the host. It has been reported that high numbers of tumor-infiltrating Tregs might be associated with poor clinical outcomes for several malignant tumors. Therefore, this study aimed to examine the impact of tumor-infiltrating Tregs on the prognosis of gastric carcinoma patients.
METHODS
The immunohistochemical staining for anti-fork head Box P3 (FoxP3) antibody was performed by using a 3 mm core from the tumor specimens of each of the 173 gastric cancer patients for constructing a tissue microarray. FoxP3-positive Tregs were quantified by calculating the numbers of positive cells per 5 high-power fields on light microscopy. Thereafter, the 173 patients were subdivided into the low Tregs group (< or = 3/5 high power fields [HPF], n = 41) and the high Tregs group (> 3/5 HPF, n = 132).
RESULTS
The high Tregs group was significantly associated with a higher stage, more invasion depth and lymph node metastasis (p = 0.009, p = 0.036, p = 0.006, respectively). The high Tregs group showed significantly poorer overall survival and event-free survival (p = 0.004, p = 0.017, respectively) on the univariate analysis. The Tregs group and the tumor, node and metastasis stage were also independent prognostic factors that were significantly associated with overall survival (p = 0.025, p < 0.001, respectively) by multivariate analysis.
CONCLUSIONS
Our results indicated that a high number of tumor-infiltrating FoxP3-positive Tregs could be an indicator of poor long term survival for gastric carcinoma patients. -
Citations
Citations to this article as recorded by- Tumor-infiltrating PD1-Positive Lymphocytes and FoxP3-Positive Regulatory T Cells Predict Distant Metastatic Relapse and Survival of Clear Cell Renal Cell Carcinoma
Myoung Jae Kang, Kyoung Min Kim, Jun Sang Bae, Ho Sung Park, Ho Lee, Myoung Ja Chung, Woo Sung Moon, Dong Geun Lee, Kyu Yun Jang
Translational Oncology.2013; 6(3): 282. CrossRef - Significance of Foxp3 Positive Regulatory T Cell and Tumor Infiltrating T Lymphocyte in Triple Negative Breast Cancer
Hanna Kang, Harin Cheong, Min Sun Cho, Heasoo Koo, Woon Sup Han, Kyung Eun Lee, Byung In Moon, Sun Hee Sung
The Korean Journal of Pathology.2011; 45(1): 53. CrossRef
- Tumor-infiltrating PD1-Positive Lymphocytes and FoxP3-Positive Regulatory T Cells Predict Distant Metastatic Relapse and Survival of Clear Cell Renal Cell Carcinoma
- Expression of Survivin in Gastric Carcinoma and its Relation to Tumor Cell Proliferation and Apoptosis.
- Wan Sik Lee, Sung Bum Cho, Jong Sun Rew, Jae Hyuk Lee, Chang Soo Park, Young Eun Joo
- Korean J Pathol. 2009;43(4):329-334.
- DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.329
- 4,136 View
- 43 Download
- 1 Crossref
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Abstract
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- BACKGROUND
Survivin, a novel antiapoptotic gene has been linked with tumor development and progression in various human carcinomas including gastric carcinomas. The aim of this study was to evaluate the expression of survivin in gastric carcinoma and its correlation with tumor cell proliferation and apoptosis. METHODS: Expression of survivin was evaluated immunohistochemically in 84 surgically resected gastric carcinomas. Tumor cell apoptosis was evaluated with terminal deoxynucleotidyl transferase (TdT) mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL), and Ki-67 immunostaining was used for evaluation of tumor cell proliferation. RESULTS: Expression of survivin was noted in 53.6% of the gastric carcinomas, and was significantly associated with depth of invasion, status of lymph node metastasis or tumor stage (p=0.022, 0.034, 0.040, respectively). There was an inverse correlation between survivin expression and apoptotic index (p=0.015). But there was no significant correlation between survivin expression and Ki-67 labeling index (p=0.430). CONCLUSIONS: These results suggest that survivin expression may contribute to tumor development and progression by inhibiting apoptosis in human gastric carcinoma. -
Citations
Citations to this article as recorded by- Significance of intracellular localization of survivin in cervical squamous cell lesions: Correlation with disease progression
SOO-AH KIM, RAN HONG
Oncology Letters.2014; 7(5): 1589. CrossRef
- Significance of intracellular localization of survivin in cervical squamous cell lesions: Correlation with disease progression
- beta-Catenin Expression in Gastric Carcinogenesis.
- Haeyoun Kang, Yon Rak Choi, Hoguen Kim
- Korean J Pathol. 2001;35(5):376-382.
- 2,100 View
- 17 Download
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Abstract
PDF
- BACKGROUND
The molecular pathogenesis of gastric carcinoma is not yet well characterized. The purpose of this study is to assess the role of beta-catenin in gastric carcinogenesis.
METHODS
We analyzed beta-catenin expression using immunohistochemistry on 68 gastric adenomas and 34 gastric adenocarcinomas, and compared the result with pathological and molecular types of tumors and E-cadherin expression.
RESULTS
Nuclear expression of beta-catenin was noted more frequently in gastric adenomas than in carcinomas (40% vs. 21%, 0.05< or = P<1). There was no significant relationship between nuclear beta-catenin expression and histologic degree of adenoma, histologic type of carcinoma or microsatellite instability. E-cadherin expression showed significantly more frequent decrease in the membrane stainability of carcinomas compared to adenomas (P<0.01).
CONCLUSIONS
The frequent nuclear beta-catenin expression in gastric adenomas suggests that the beta-catenin alteration might play an early role in gastric carcinogenesis.
- CD24 Expression in Gastric Adenocarcinoma Is Associated with Tumor Invasiveness.
- Kyeong Cheon Jung, Jae Nam Seo, Tae Woon Kim, Young Mi Choi, Kwon Ik Oh, Hun Ho Song, Hyung Sik Shin, Young Euy Park
- Korean J Pathol. 2004;38(6):388-393.
- 2,331 View
- 17 Download
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Abstract
PDF
- BACKGROUND
CD24, also referred to as the heat stable antigen in mice, is a glycosyl phosphatidylinositol- linked glycoprotein expressed by thymocytes, B cells, neutrophils and immature neuronal cells. It has been recently observed in a variety of human malignancy. Here, we demonstrated the expression of CD24 in gastric adenocarcinomas.
METHODS
A total of 40 gastric adenocarcinomas and 20 tubular adenomas were immunohistochemically examined for the expression of CD24 and matrix metalloproteinase-2 (MMP-2) proteins. The immunoreactivity of CD24 was semiquantitatively scored (0, 1+, 2+) and compared with clinicopathologic variables and MMP-2 expression in tumor cells.
RESULTS
CD24 was rarely expressed in normal gastric tissue and not expressed in tubular adenoma. In contrast, a moderate/strong expression (2+) of CD24 was observed in 25% of gastric adenocarcinomas, and 30% cases showed a weak CD24 staining (1+). Moreover, CD24 expression was significantly correlated with the depth of tumor invasion and MMP-2 expression.
CONCLUSION
These results suggest that the aberrant expression of CD24 in gastric adenocarcinomas might be associated with tumor progression and invasiveness.
Case Report
- Triple Synchronous Cancers of Stomach, Pancreas, and Kidney.
- Seung Koo Lee, Byung Ha Choi, Shin Kwang Khang, Byung Sik Kim, Jooryung Huh
- Korean J Pathol. 2001;35(6):547-550.
- 2,052 View
- 10 Download
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Abstract
- Synchronous occurrence of triple distinct malignant tumors in the same patient is very rare. We report a unique case of a triple cancer occurring in a 70-year-old Korean woman with synchronous signet ring cell carcinoma of the stomach, renal cell carcinoma of the conventional type of the left kidney, and invasive ductal adenocarcinoma and intraductal papillary carcinoma of the pancreas. All three cancers were successfully resected simultaneously by total gastrectomy, nephrectomy, and partial pancreatectomy with corresponding lymphadenectomies. This patient tolerated these surgical procedures well and led a normal healthy life during the 18 months of follow-up. In summary, a successful resection of synchronous triple cancers which has never been previously reported in such combination, is described.
Original Article
- Correlation Between Expression of p53, Bcl-2 Protein and Ki-67 Labelling Index and Lymph Node Metastasis in Early Gastric Cancer.
- Joon Hyuk Choi, Young Ran Shim
- Korean J Pathol. 2002;36(1):7-12.
- 2,365 View
- 41 Download
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Abstract
PDF
- BACKGROUND
The purpose of this study was to investigate the difference of cliniopathological variables and p53, bcl-2, and Ki-67 labelling index between early gastric cancer with and without lymph node metastasis.
METHODS
The authors analyzed thirty patients who had early gastric cancer confined to submucosa (sm cancer) without lymph node metastasis and thirty patients who had sm cancer with lymph node metastasis. The expression of p53 protein, bcl-2 protein and Ki-67 labelling index were evaluated by immunohistochemistry.
RESULTS
No significant correlation was found between lymph node metastasis and age, sex, tumor size, Lauren classification, histologic grade, and venous invasion. But lymphatic invasion was significantly correlated to lymph node metastasis (p<0.01). The p53 positive rate was 73.3% (22/30) and 66.7% (20/30) in sm cancer with and without lymph node metastatsis, respectively. The bcl-2 positive rate was 40.0% (12/30) and 30.0% (9/30) in sm cancer with and without lymph node metastasis, respectively. The Ki-67 labelling index (%) was 63.9+/-15.3 and 61.4+/-12.8 in sm cancer with and without lymph node metastasis, respectively. The lymph node metastasis was not significantly correlated to expression of p53 protein, bcl-2 protein or Ki-67 labelling index.
CONCLUSIONS
Expression of p53, bcl-2 protein and proliferative activity of sm cancer may not influence lymph node metastasis. Lymphatic invasion is a significant predictor of lymph node metastasis.
Case Report
- Primary Choriocarcinoma of the Stomach: A Case Report.
- Eun Joo Seo, Hi Jeong Kwon, Ki Ouk Min, Keun Woo Lim, Seong Lee, Byung Kee Kim
- Korean J Pathol. 2002;36(1):55-58.
- 2,123 View
- 14 Download
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Abstract
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- A case of primary gastric choriocarcinoma with multiple liver metastases is described. A 54-year-old man underwent gastrectomy for an advanced cancer. An ulcerofungating tumor with extensive hemorrhagic necrosis was found in the anterior wall of the prepyloric antrum. The histologic examination revealed a biphasic pattern composed of uninucleated cyto or intermediate trophoblasts and syncytiotrophoblasts. A small area of the adenocarcinoma forming glandular structures and poorly differentiated solid sheets was also noted on the superficial portion of the tumor. Immunohistochemical staining for the beta human chorionic gonadotropin (-hCG) and the human placental lactogen (hPL) showed strong immunoreactivity, particularly in the cytoplasms of the syncytiotrophoblasts and intermediate trophoblasts, respectively. A diagnosis of the choriocarcinoma was made. Multiple hepatic nodules consistent with metastases were noted on the abdominal sonogram. The serum -hCG level of the patient was significantly increased.
Original Articles
- Ras Gene Mutations and Expression of ERK1 and ERK2 Proteins in Stomach Cancer.
- Jinyoung Yoo, Seok Jin Kang, Byung Kee Kim, Chang Suk Kang
- Korean J Pathol. 2002;36(2):77-83.
- 2,081 View
- 14 Download
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Abstract
PDF
- BACKGROUND
We investigated stomach cancers for ras abnormalities and expression of ERK1 and ERK2 to determine their significance in the tumor development and/or progression and to evaluate their potential correlation with clinicopathologic parameters.
METHODS
Seventy gastric adenocarcinomas were studied immunohistochemically in paraffin-embedded tissue sections for the expression of ERK1 and ERK2 proteins. All tumors were further analyzed with the use of a polymerase chain reaction technique and a direct sequence analysis procedure for the presence of the mutated ras gene.
RESULTS
ERK1 and/or ERK2 was expressed in 65.7% (46/70) of the tumors; overexpression of ERK1 was observed in 38 (54.3%) tumors, whereas ERK2 was detected in 29 (41.4%). Nine (12.8%) samples demonstrated multations in the ras gene: 4 in H-ras and 5 in K-ras. Seven of the 9 (77.8%) mutated tumors were of the intestinal type. No association was established between the ras abnormalities and the overexpression of ERK1 and/or ERK2. However, the correlation between ERK2 and progression (early vs. advanced) was statistically significant (p<0.05).
CONCLUSIONS
These data indicate that ras abnormalities are uncommon events in gastric adenocarcinomas. The majority of ras mutations, however, occurred in intestinal-type tumors, supporting the notion of different molecular mechanisms involved between the intestinal-and diffuse-type lesions. Enhanced ERK2 activity may provide assistance in the determination of tumor penetration in these tumors.
- Expression of Nitric Oxide Synthase Isotypes in Advanced Gastric Carcinoma.
- Kyong Mee Kwon, Young Chae Chu, Tae Sook Hwang
- Korean J Pathol. 2002;36(6):374-371.
- 1,922 View
- 11 Download
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Abstract
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- BACKGROUND
Increased expression of nitric oxide synthase (NOS) isotypes is present in human tumor cell lines and solid tumor tissues. Hypoxia upregulates NOS expression, and nitric oxide (NO) induces mitogenesis among endothelial cells. NO has been known to induce vascular endothelial growth factor (VEGF) expression in carcinoma cells and to induce neovascularization in tumors.
METHODS
The expression and cellular localization of 3 isotypes of NOS was detected by immunohistochemistry in 73 advanced gastric carcinoma tissues along with adjacent normal gastric mucosa; and the relationship to known clinicopathologic parameters, microvascular density, and VEGF expression was analysed.
RESULTS
Forty-four (60.3%), 56 (76.7%), and 52 (71.2%) of the 73 cases revealed eNOS, nNOS, and iNOS expression, respectively. Intestinal type adenocarcinomas tended to have higher activity of eNOS (p=0.000) and nNOS (p=0.001) activities than did the diffuse type adenocarcinomas. All isotypes of NOS (eNOS, p=0.001; nNOS, p=0.005; iNOS, p=0.044) tended to be highly expressed when the tumor was differentiated. There was no significant relationship between any of the 3 NOS isotypes and microvascular density, whereas VEGF was closely related with microvascular density (p=0.000). The expression of VEGF was not related to with any of the NOS isotype expressions.
CONCLUSIONS
From the above results, we speculated that NO may be implicated in the early stage of the gastric carcinogenesis rather than the growth and progression stages, and NO does not appear to affect angiogenesis or VEGF expression in the advanced gastric carcinoma.
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