Journal of Pathology and Translational Medicine

Original Articles

Elevated expression of Axin2 in intestinal metaplasia and gastric cancers: Dong Hui Lee, In Ho Jeong, Bogun Jang; J Pathol Transl Med. 2023;57(6):315-322. Published online November 7, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.12

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Background
The Wnt signaling pathway regulates crucial cellular processes, including stem cell development and tissue repair. Dysregulation of this pathway, particularly β-catenin stabilization, is linked to colorectal carcinoma and other tumors. Axin2, a critical component in the pathway, plays a role in β-catenin regulation. This study examines Axin2 expression in normal gastric mucosa and various gastric pathologies.
Methods
Formalin-fixed and paraffin-embedded tissue samples from normal stomach, gastritis, intestinal metaplasia (IM), and gastric carcinoma were collected. Axin2 and β-catenin expression were evaluated using RNA in situ hybridization and immunohistochemistry, respectively. Histo-scores (H-scores) were calculated to quantify expression levels of Axin2. Associations between Axin2 expression and clinicopathological variables were examined.
Results
Axin2 expression was examined in normal stomach, gastritis, and IM tissues. Axin2 expression was mainly observed in the surface and isthmus areas in the normal stomach and gastritis, whereas Axin2 expression was markedly higher at the bases of IM. Axin2 H-scores were significantly elevated in IM (mean ± standard deviation [SD], 87.0 ± 38.9) compared to normal (mean ± SD, 18.0 ± 4.5) and gastritis tissues (mean ± SD, 33.0 ± 18.6). In total, 30% of gastric carcinomas showed higher Axin2 expression. Axin2 expression did not have significant associations with age, sex, Lauren classification, histological differentiation, invasion depth, and lymph node metastasis. However, a strong positive correlation was observed between Axin2 and nuclear β-catenin in gastric carcinomas (p < .001).
Conclusions
Axin2 expression was significantly increased in IM compared to normal and gastritis cases. In addition, Axin2 showed a strong positive association with nuclear β-catenin expression in gastric carcinomas, demonstrating a close relationship with abnormal Wnt/β-catenin signaling pathway.

Citations

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A review of potential mechanisms and treatments of gastric intestinal metaplasia
Yueyao Wu, Kehan Zhang, Yichao Zheng, Haifeng Jin
European Journal of Gastroenterology & Hepatology.2025; 37(4): 383. CrossRef
Refining NTRK Fusion Detection in Papillary Thyroid Carcinoma Through Pan-TRK Immunohistochemistry and Histopathologic Features
Hyun Lee, Sue Youn Kim, Ji Min Park, Seung-Hyun Jung, Ozgur Mete, Chan Kwon Jung
Endocrine Pathology.2025;[Epub] CrossRef
AXIN2 variants, tooth agenesis, and cancer risk: a systematic review
Nutthakarn Ratanasereeprasert, Narin Intarak, Chayanit Chaweewannakorn, Mushriq Abid, Anand Marya, Sung-dae Cho, Thantrira Porntaveetus
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Journal of Medicinal Chemistry.2025; 68(24): 26085. CrossRef
Listening to the Past, Shaping the Future: A Data-mining Based and Visual Analysis of Five Decades of Gastric Carcinogenesis Research
Tai Zhang, Xudong Tang
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Postbiotics Combination Synergises the Antiproliferative Effects of Doxorubicin in Gastric Cancer Cells: A Cellular and Molecular Deep Dive
Radwa A. Eladwy, Mohamed Fares, Muhammad A. Alsherbiny, Dennis Chang, Chun-Guang Li, Deep Jyoti Bhuyan
International Journal of Molecular Sciences.2025; 27(1): 362. CrossRef

MUC2 Expression Is Correlated with Tumor Differentiation and Inhibits Tumor Invasion in Gastric Carcinomas: A Systematic Review and Meta-analysis: Jung-Soo Pyo, Jin Hee Sohn, Guhyun Kang, Dong-Hoon Kim, Kyungeun Kim, In-Gu Do, Dong Hyun Kim; J Pathol Transl Med. 2015;49(3):249-256. Published online May 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.03.27

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Abstract PDF

Background
While MUC2 is expressed in intestinal metaplasia and malignant lesions, the clinico-pathological significance of MUC2 expression is not fully elucidated in gastric carcinoma (GC). Methods: The present study investigated the correlation between MUC2 expression and clinico-pathological parameters in 167 human GCs. In addition, to confirm the clinicopathological significance of MUC2 expression, we performed a systematic review and meta-analysis in 1,832 GCs. Results: MUC2 expression was found in 58 of 167 GCs (34.7%). MUC2-expressing GC showed lower primary tumor (T), regional lymph node (N), and tumor node metastasis (TNM) stages compared with GCs without MUC2 expression (p=.001, p=.001, and p=.011, respectively). However, MUC2 expression was not correlated with Lauren’s classification and tumor differentiation. In meta-analysis, MUC2 expression was significantly correlated with differentiation and lower tumor stage (odds ratio [OR], 1.303; 95% confidence interval [CI], 1.020 to 1.664; p = .034 and OR, 1.352; 95% CI, 1.055 to 1.734; p = .017, respectively) but not with Lauren’s classification, pN stage, or pTNM stage. Conclusions: MUC2 expression was correlated with a lower tumor depth and lower lymph node metastasis in our study; the meta-analysis showed a correlation of MUC2 expression with tumor differentiation and lower tumor depth.

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Prognostic and clinicopathological significance of mucin family members expression in gastric cancer: a meta-analysis
Shunda Wang, Yongrun Mu, Jianwei Zhang, Chengfeng Wang
Frontiers in Oncology.2025;[Epub] CrossRef
Diagnostic gastrointestinal markers in primary lung cancer and pulmonary metastases
Karina Malmros, Andreas Lindholm, Halla Vidarsdottir, Karin Jirström, Björn Nodin, Johan Botling, Johanna S. M. Mattsson, Patrick Micke, Maria Planck, Mats Jönsson, Johan Staaf, Hans Brunnström
Virchows Archiv.2024; 485(2): 347. CrossRef
Gastric epithelial histology and precancerous conditions
Hang Yang, Wen-Juan Yang, Bing Hu
World Journal of Gastrointestinal Oncology.2022; 14(2): 396. CrossRef
COX-2 strengthens the effects of acid and bile salts on human esophageal cells and Barrett esophageal cells
Shen Jiangang, Kang Nayoung, Wang Hongfang, Li Junda, Chen Li, Bai Xuefeng, Li Mingsong
BMC Molecular and Cell Biology.2022;[Epub] CrossRef
Comparative genomic analysis of primary tumors and paired brain metastases in lung cancer patients by whole exome sequencing: a pilot study
Pascale Tomasini, Fabrice Barlesi, Sophie Gilles, Isabelle Nanni-Metellus, Riccardo Soffietti, Emilie Denicolai, Eric Pellegrino, Emilie Bialecki, L’Houcine Ouafik, Philippe Metellus
Oncotarget.2020; 11(50): 4648. CrossRef
A High Ki67/BCL2 Index Could Predict Lower Disease-Free and Overall Survival in Intestinal-Type Gastric Cancer
Kyueng-Whan Min, Dong-Hoon Kim, Byoung Kwan Son, Dong Hyun Kim, Eun-Kyung Kim, Jinwon Seo, Sang Bong Ahn, Yun Ju Jo, Young Sook Park, Junghoon Ha
European Surgical Research.2017; 58(3-4): 158. CrossRef

Prognostic Significance of Heat Shock Protein 70 Expression in Early Gastric Carcinoma: Youngran Kang, Woon Yong Jung, Hyunjoo Lee, Wonkyung Jung, Eunjung Lee, Bong Kyung Shin, Aeree Kim, Han Kyeom Kim, Baek-hui Kim; Korean J Pathol. 2013;47(3):219-226. Published online June 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.219

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Abstract PDF

Background

Overexpression of heat shock protein 70 (HSP70) has been observed in many types of cancer including gastric adenocarcinomas, although the exact role of HSP70 in carcinogenesis remains unclear.

Methods

The study analyzed a total of 458 radical gastrectomy specimens which were immunohistochemically stained with HSP70, p53, and Ki-67 antibodies.

Results

The study determined that the expression of HSP70 was significantly increased in early gastric cancer (EGC) compared to advanced gastric cancer (p<0.001). The HSP70 expression was correlated with well-differentiated tumor type, intestinal type of Lauren classification and the lower pT and pN stage. Negative expression of Ki-67 and p53 expression was associated with poor prognosis. The study did not find any correlation between HSP70 and p53 expression. The study determined that HSP70 expression in the EGC subgroup was associated with a poor prognosis (p=0.009), as well as negative Ki-67 expression (p=0.006), but was not associated with p53. Based on multivariate analysis, HSP70 expression (p=0.024), negative expression of Ki-67, invasion depth and lymph node metastasis were determined to be independent prognostic markers.

Conclusions

HSP70 is expressed in the early stages of gastric adenocarcinoma. In EGC, HSP70 is a poor independent prognostic marker and is correlated with a low proliferation index.

Citations

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Journal of Gastrointestinal Cancer.2024; 55(2): 599. CrossRef
Clinicopathological significance of HSP70 expression in gastric cancer: a systematic review and meta-analysis
Xiaolu Wang, Li Xie, Lijing Zhu
BMC Gastroenterology.2021;[Epub] CrossRef
Beta-sheet-specific interactions with heat shock proteins define a mechanism of delayed tumor cell death in response to HAMLET
Aftab Nadeem, James C.S. Ho, Tuan Hiep Tran, Sanchari Paul, Victoria Granqvist, Nadege Despretz, Catharina Svanborg
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Shubhi Srivastava, Vinaya Vishwanathan, Abhijit Birje, Devanjan Sinha, Patrick D’Silva
Critical Reviews in Biochemistry and Molecular Biology.2019; 54(6): 517. CrossRef
Clinicopathologic significance and prognostic value of Ki-67 expression in patients with gastric cancer: a meta-analysis
Guanying Luo, Yunzhao Hu, Zhiqiao Zhang, Peng Wang, Zhaowen Luo, Jinxin Lin, Canchang Cheng, You Yang
Oncotarget.2017; 8(30): 50273. CrossRef
Extracellular HSP70-peptide complexes promote the proliferation of hepatocellular carcinoma cells via TLR2/4/JNK1/2MAPK pathway
Yi Zhe, Yan Li, Dan Liu, Dong-Ming Su, Jin-Gang Liu, Hang-Yu Li
Tumor Biology.2016; 37(10): 13951. CrossRef
The cytomegalovirus protein UL138 induces apoptosis of gastric cancer cells by binding to heat shock protein 70
Wenjing Chen, Kezhi Lin, Liang Zhang, Gangqiang Guo, Xiangwei Sun, Jing Chen, Lulu Ye, Sisi Ye, Chenchen Mao, Jianfeng Xu, Lifang Zhang, Lubin Jiang, Xian Shen, Xiangyang Xue
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Targeting the hsp70 gene delays mammary tumor initiation and inhibits tumor cell metastasis
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A Study on Total Lactic Dehydrogenase (LD) Activity and Its Isoenzymes in Neoplastic Tissue of Stomach Carcinoma.: Seo Hee Rha, Sun Kyung Lee; Korean J Pathol. 1989;23(3):279-286.

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Abstract PDF: This sutdy was performed to find out a LD isoenzyme pattern in neoplastic tissue of gastric carcinoma and in gastric mucosa with intestinal metaplasia, which has been known as premalignant lesion. The specimens used in this study were 18 stomachs with caarcinoma and 8 stomachs with peptic ulcer as control, and wer obtained by subtotal or total gastrectomy at Pusan National University Hsopital from Oct. 1987 to Sept. 1988. Total LD activity and its isoenzymes in body and antral mucosae and neoplastic tissue of stomach were assayed, and analysed statistically from several points of view. The results obtained were summarized as follows: 1) There was no significant difference in total LD activity between univolved body and antral mucosae of stomach with carcinoma, and between mucosa of stomach with peptic ulcer and univolved mucosa of stomach with carcinoma. 2) Total LD activity in the neoplastic tissue of gastric carcinoma was significantly higher than those of univolved body and antral mucosae of stomach with carcinoam or that of stomach with peptic ulcer, but no significant difference was observed among histological types of gastric carcinoma. 3) The uninvolved body mucosa of stomach with carcinoma or peptic ulcer showed a pattern of LD1 predominance and increas of H to M ratio, while the antral mucosa of stomach with carcinoma or peptic ulcer showed a pattern of LD3 predominance and decrease of H to M ratio. 4) The LD4 and LD5 fractions in antral mucosa with moderate to severe intestinal metaplasia were slightly increased than those of antral mucosa with nil to mild intestinal metaplasia, but did not show statistically significant difference. 5) Marked increase of LD5 fraction was found in neoplastic tissue of gastric carcinoma, and thus ratio of H to M subunit in neoplastic tissue was significantly lower, as compared with body or antral univolved mucosa of stomach. In conclusion, the neoplastic tissue of gastric carcinoma and gastric mucosa with intestinal metaplasia show substantially predominant "M" subunit as well as increased total LD activity.

Eosinophilic Liver Abscess in Patients with Gastric Carcinoma.: Soon Won Hong, Ho Guen Kim, Chan Il Park, Sang In Lee; Korean J Pathol. 1993;27(1):27-33.

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Abstract PDF: Sixteen cases of heavy eosinophil infiltration or eosinophilic abscess of the liver in patients with gastric carcinoma were analyzed to draw attention to this interesting combination and to persue the pathogenetic mechanism. Peripheral blood eosinophilia and hepatic granuloma were found in only 5 and 4 cases, respectively. Neither the patients' stool nor the hepatic tissues disclosed any parasitic worms or eggs, although the skin tests for Clonorchis sinensis and Paragonimus westermani were positive in 2 cases. Among stomach carcinomas, early gastric cancer tended to have more eosinophils than advanced carcinoma, but was less frequently associated with the infiltration of mast cells. In the regional lymph nodes, there was no infiltration of eosinophils even in the presence of tumor metastasis. In the liver, none of the 16 cases had metastatic gastric carcinoma and mast cells were found in only 2 cases. The results suggest that heavy hepatic infiltration of eosinophils in gastric carcinoma patients is not of the parasitic or allergic cause, but of certain eosinophil chemotactic factor which may gain access to accumulate in the liver following released from the gastric carcinoma and transfered through the portal vein.

Immunohistochemical Study of the Vascular Endothelial Growth Factor in Gastric Carcinoma.: Tae Jung Jang, Jung Ran Kim; Korean J Pathol. 1997;31(5):401-409.

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Abstract PDF: Many studies have shown that angiogenesis plays an important role in the growth, the progression, and the metastasis of a solid tumor. The vascular endothelial growth factor(VEGF) is thought to be a selective mitogen for endothelial cells. Twenty eight advanced gastric carcinomas and twenty early gastric carcinomas were investigated by staining with polyclonal antibody against the VEGF. Correlation between the expression of the VEGF and the clinicopathologic features of gastric carcinoma were studied. The VEGF was mainly localized to the cytoplasm of carcinoma cells. Normal gastric foveolar epithelium was not immunoreactive, but some endothelial cells were weakly immunoreactive with an anti-VEGF antibody. Expression of the VEGF was significantly higher in advanced gastric carcinoma than in early gastric carcinoma (p=0.003). Expression of the VEGF was correlated with the depth of tumor, the lymph node metastasis, and the stage (p<0.05). The VEGF positivity was significantly higher in moderately and poorly differentiated gastric carcinoma than in well differentiated gastric carcinoma. The VEGF scores of the metastatic foci in the lymph nodes were higher than that of the primary tumors, which were followed by deep and superficial portions of the primary tumors in a descending order (p<0.05). In summary, the expression of the VEGF may be associated with progression and metastasis of a gastric carcinoma and may also be a good prognostic factor in a gastric carcinoma.

Immunohistochemical Study of E-cadherin Expression in Gastric Adenocarcinomas.: Jee Yeon Kim, Mee Young Sol, Sun Kyung Lee; Korean J Pathol. 1997;31(8):745-753.

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Abstract PDF: E-cadherin (ECD) is a Ca++ -dependent adhesion molecule which plays a major role in the maintenance of intercellular adhesion in epithelial tissues. The expression pattern of ECD in 77 surgically resected gastric adenocarcinomas was examined by immunohistochemistry, using a rat monoclonal antibody raised against murine E-cadherin (DECAM-1). ECD was strongly expressed uniformly at cell to cell borders in normal gastric epithelium without exception. But, various staining patterns were observed in the cancer tissues. The frequency of tumors with preserved ECD expression (Pre-type) and reduced ECD expression (Rd-type) was 44% and 56%, respectively. Using Lauren's classification, the high frequency of the Pre-type expression in adenocarcinoma of the intestinal type was significantly higher than that in adenocarcinoma of the diffuse type (p<0.05). But, no significant correlation between the ECD expression and the gross type, invasion depth, growth pattern or metastasis was observed. These results suggest that ECD might play a key role in the morphogenesis of gastric adenocarcinoma.

Pathological and Epidemiological Analysis of Gastric Carcinoma among Koreans in Pusan Area.: Sook Nyo Lee, Dongsoo Suk, Yeon Jae Cheong, Sun Kyung Lee; Korean J Pathol. 1990;24(4):375-385.

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Abstract PDF: Epidemiology, pathology, diagnosis and treatment of gastric carcinoma has been revised recently. The authors analysed 3,170 cases of gastric carcinoma which were diagosed with fiberoptic biopsy or resected specimens from 1968 to 1988 in Pusan area. The specimen were collected from Pusan National University Hospital, Pusan Paik Hospital and other general hospitals in Pusan city. The results obtained were summarized as follows; 1) The time trend indicated that difference in the annual fluctuation of requency of gastric carcinoma during last 21 years was not statistically significant. But it was noticed that by comparing the following the two decades (1970~1979 and 1980~1988) the frequency of gastric carcinoma decreased in male, in middle age and in intestinal type. 2) Morbidity of gastric carcinoma increased in both sexes by aging, and this tendency was more marked in male and in intestinal type in female and in diffuse type. 3) In general the gastric carcinoma involved more frequently distal portion than proximal portion of the stomach was characterized predominantly by male, older patients and intestinal type. 4) Carcinoma with Borrmann type I and II were characterized predominantly by male, older patients and intestinal type. With Borrmann type III and IV, female, young patients and diffuse type were found more frequently. From the above results, the authors concluded that the pathological and epidemiological findings of gastric carcinoma among Koreans in Pusan area showed a transition moving from high risk to low risk area of gastric carcinoma.

Plasma prostaglandin E2 Levels in Patients wth Gastric Carcinoma.: Gyeong Yeob Gong, Sun Kyung Lee; Korean J Pathol. 1990;24(4):386-392.

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Abstract PDF: This study was performed for the purpose of evaluation of plasma PGE2, levels in patients with gastric carcinomas. To carry out this study twenty-one gastrectomy patients with gastric carcinoma were selected. Serial plasma PGE2 levels were measured before and after operation by radioimmunoassay. Plasma PGE2 was also measured in five normal healthy volunteers or of patients with gastric ulcer. The conclusion drawn therefrom were as followed: 1) In normal healthy volunteers, plasma PGE2 level was 50.2+/-16.5 pg/ml which ws higher than that of parients with gastric ulcer, 20.7+/-15.4 pg/ml, (p<0.001). 2) In patients with diffuse type of gastric carcinoma, preoperative and postoperative plasma PGE2 levels were 25.7+/-12.1 pg/ml, and 23.1+/-8.7 pg/ml, rewpectively. In parients with intestinal type of gastric carcinoma, preoperative and postoperastive plasma PGE2 levels were 26.2+/-8.9 pg/ml and 24.1+/-11.2 pg/ml, respectively. In both types of gastric carcinoma, plasma PGE2 levels were lower than that of normal healthy volunteers and there was no significant difference compaired with the levels in patients with gastric ulcer. 3) In diffuse and intestinal types of gastric carcinoma, postoperative PGE2 levels were lower that those of preoperative state but it was not significant. 4) In early and advanced gastric carcinoma, preoperative PGE2 levels were 29.0+/-11.7 pg/ml and 24.8+/-9.9 pg/ml, respectively. There was no significant difference by the depth of invasion. From the result as mentioned above, it is concluded that plasma PGE2 levels of patients with gastric carcinoma and it is presumable that there is a factor decreasing plasma PGE2 levels in patients with gastric carcinoma or ulcer.

A Study of the Correlation between Prognostic Factors of Human Gastric Carcinomas and the Expression of CD44.: Ho Lee, Hyung Chul Kim, Woo Sung Moon, Myoung Jae Kang; Korean J Pathol. 1997;31(9):873-883.

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Abstract PDF: This study was performed to investigate the relationship between CD44 expression and depth of, tumor invasion histopathologic differentiation, tumor size, lymph node metastasis, and proliferating capacity of tumor cells in the gastric carcinoma. In 20 cases of early gastric carcinoma (EGC) and 40 cases of advanced gastric carcinoma (AGC), the immunohistochemical staining for CD44v3, CD44v5, and PCNA gave the following results. 1) In all 60 cases, the positive rates for CD44v3 and CD44v5 were 18.3% and 71.7%, respectively. 2) CD44v5 was expressed in 45% of EGC and 85% of AGC. 3) Larger tumors exhibited higher positive rates for CD44v5. 4) There were 28 cases of lymph node metastases out of 43 cases of CD44v5- positive primary gastric carcinomas (65.1%), and there were 4 cases of lymph node metastases out of 17 CD44v5-negative cases (23.5%). 5) There was no relationship between CD44v5 expression and PCNA index. Because the tumors that exhibit deep invasion, and large in size and have lymph node metastses tend to have more frequent expression of CD44v5, CD44v5 may be one of the useful prognostic markers for gastric carcinoma.

Gastric Carcinoma with Lymphoid Stroma: Pathologic and immunohistochemical study of 14 cases.: Eun Hee Lee, Woo Young Jang, Kyoung Chan Choi, Young Ran Shim, Joon Hyuk Choi, Won Hee Choi; Korean J Pathol. 1996;30(2):115-120.

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Abstract PDF: A total of 672 surgically resected gastric carcinomas were reviewed, and fourteen cases(2.1%) of "gastric carcinoma with lymphoid stroma" were identified. The tumor was located mostly in cardia and body portion(86%). Thirteen patients one was lost to follow up were alive without recurrence of tumor. Grossly, this carcinoma was characterized by an expanding growth pattern or a multinodular pattern. Histologically, this carcinoma showed an irregular trabecular and alveolar arrangement and densely infiltrated lymphoid cells with lymph follicles. The tumor cell nests were widely separated by non-desmoplastic lymphoid stroma. On immunohistochemical study, T cells were evenly distributed throughout the tumor lesion with intimate contact with individual carcinoma cells, but B cells were mainly present within the germinal centers of lymph follicles. Thus, the organized immune response combined with cell mediated and humoral immunities against the carcinoma cells may be a defense mechanism of the host in this type of gastric carcinoma.

Correlation between p53 Immunohistochemical Expression, DNA Ploidy and Ki-67 Expression in Gastric Carcinoma.: Young Lyun Oh, Joung Ho Han, Young Hyeh Ko, Cheol Keun Park, Hwoe J Ree; Korean J Pathol. 1997;31(12):1264-1271.

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Abstract PDF: We examined the p53 protein overexpression and evaluated its correlation with pathobiological variables, including: (1) patient age, sex, tumor size, histological type and grade, invasion depth, vascular invasion, perineural invasion and lymph node status; (2) the Ki-67 labeling index in 100 gastric carcinomas; and (3) the DNA ploidy pattern, S phase fraction (SPF), and the proliferation index (PI) in 84 cases using flow cytometry. The positive rate of p53 staining was 48% and the p53 immunoreactivity was independent of variable clinicopathologic factors. No correlation was made between the Ki-67 labeling index with p53 immunostaining and DNA ploidy parameters. Aneuploidy rate was slightly higher in the p53 positive group (55.6%) than the p53 negative group (44.4%)(p=0.097). The mean values of SPF and PI were significantly higher in the p53 protein positive group. Aneuploidy was more often observed in the intestinal type (p=0.038), advanced gastric carcinoma (p=0.015) and lymph node positive group(p=0.039). The above results suggest that although the p53 protein overexpression has no significant correlation with pathological factors and the Ki-67 labeling index, it may play an important role in tumor cell proliferation. Since p53 protein overexpression was slightly higher in the aneuploidy group showing significant correlation with poor prognostic parameters, it is thought that re-evaluation of the p53 mutation by molecular biological study is needed.

Immunohistochemical Study of the Multidrug Resistant(MDR) Gene Expression in Gastric Carcinoma.: Jung Hee Han, Byung Gon Park, Mi Sook Roh, Sook Hee Hong; Korean J Pathol. 1994;28(1):38-48.

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Abstract PDF: We performed immunohistochemical stain of p-glycoprotein using JSB-1 monoclonal antibody to study multidrug resistant(MDR) gene expression in 137 gastric tumor tissues obtained from 87gastric carcinoma patients. The incidence of p-glycoprotein expression was 60 of 87 cases(69%) and it was not correlated with age, sex, depth of tumor invasion, and lymph node metastasis, but was correlated with histologic type of gastric adenocarcinoma. The distribution of p-glycoprotein positive cells in the tumor tissue was diffuse in 34 cases(73.9%) and focal in 12 cases(26.1%), and the dominant staining patterns of p-glycoprotein in the tumor cells were cytoplasmic and golgi staining in 20 cases(43.5%) and 19 cases(41.3%), respectively, and 7 cases(15.2%) showed fine granules in the cytoplasm. The incidence of p-glyco-protein expression in the tumor tissue was higher in A and AB blood type patients who have A antigen than in 0 and B blood type patients. Cytoplasmic staining pattern was dominant in O and B blood types and golgi staining in A and AB blood type patients. Among 27 patients 'who received chemotherapy, partial remission was noted in 9 of 11 p-glyco-protein negative patients(81.8%) and no remission or progression of the tumor was seen in 9 of 16 p-glycoprotein positive patient(56.3%). The p-glycoprotein expression in gastric carcinoma had no direct correlation with known several prognostic factors of the gastric tumor except for histologic type, and it is supposed that p-glycoprotein detection in gastric tumor tissue by immunohisto-chemical stain is a good method for predicting the response of chemotherapy, especially in p-gly-coprotein negative cases.

Expression of Epidermal Growth Factor Related Peptides, EGF-R, and c-erbB-2 and Their Relationship with the Prognostic Factors in Gastric Carcinoma.: Joo Heon Kim, Jin Wook Lee, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee; Korean J Pathol. 1999;33(11):1039-1046.

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Abstract PDF: Recent investigations have revealed that autocrine growth factors and their receptors are closely related and play an important role in controlling cancer cell growth. We performed an immunohistochemical study on the expression of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGF-R), c-erbB-2, and PCNA labelling index in 60 cases of human gastric carcinomas. TGF-alpha was detected in 38 cases (63.3%), EGF in 26 cases (43.3%), EGF-R in 44 cases (73.3%), and c-erbB-2 in 18 cases (30%). These growth factors, EGF-R and c-erbB-2, were found more often in advanced gastric cancers. The PCNA labeling index was significantly higher in tumors with the expression of EGF-R or c-erbB-2. Tumors with simultaneous expression of EGF, TGF-alpha, EGF-R and c-erbB-2 was associated with a high PCNA labeling index. A correlation was observed between the synchronous expression of growth factors and its receptors and histological differentiation. The results suggest that the expression of EGF, TGF-alpha, EGF-R and c-erbB-2 are closely related and plays an important role in the growth and progression of human gastric carcinoma.

Histopathologic Study of the Regional Lymph Nodes Reactivity in Gastric Carcinomas.: Hae Joo Nam, Won Hee Choi, Tae Sook Lee, Suk Jae Hong; Korean J Pathol. 1987;21(1):1-11.

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Abstract PDF: This study represents the immune reaction pattern of gastric carcinoma, based on the morphologic characteristics of regional lymph nodes in the cases of stomach carcinomas. The materials were obtained from the resected specimens from 100 carcinoma patients. We chose Tsakraklides' method in classification of the structure of lymph node, which are as follows: lymphocyte predominance, germinal center predominance, unstimulated and lymphocyte depletion. The incidence was as follows: lymphocyte predominance 45, germinal center predominance 32, unstimulated 21 and lymphocyte depletion 2. In the lymph nodes of peptic ulcer, lymphocyte predominance pattern was most common. The reactivity of lymph nodes is suppressed proportionally to the severity of cancers, thus the advanced case of cancer exhibited lymphocyte depletion pattern which suggests exhaustion of immune reaction. The lymphocyte predominance pattern was frequent in superficial type and expanding type of gastric carcinoma. The cancer metastasis of lymph node in lymphocyte predominance was smaller than the other type of lymph nodes, while metastasis increased progressively higher with the orders as following: lymphocyte predominance, germinal center predominance, unstimulated and lymphocyte depletion.

A Comparative Study of Immunohistochemistry and PCR-SSCP for Detection of p53 Mutation In Gastric Carcinoma.: Jong Soon Kim, Jae Hyuk Lee, Min Cheol Lee, Chang Soo Park, Sang Woo Juhung; Korean J Pathol. 1998;32(1):21-28.

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Abstract PDF: Mutation of the p53 tumor-suppressor gene in exons 4 through 9 was examined in 34 cases of primary advanced gastric cancer using PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) and the results were compared with p53 protein expression as determined by immunohistochemistry (IHC) using a monoclonal antibody(DO-1). p53 protein detected by IHC was observed in 14 cases (41.2%) and genotypic mutation detected by PCR-SSCP in exons 4-9 was observed in 13 cases (38.2%) One case showed an aberrant band on PCR-SSCP both in Exon 7 and Exon 8/9. p53 alteration detected by either IHC or PCR-SSCP was observed in 19 cases (55.9%), but only 8 cases (23.5%) showed both p53 mutation and protein expression. We also tried to obtain the correlation between relative intensity of the shifted bands on PCR-SSCP and percentage of positive cells by IHC, but a significant correlation was not seen between relative intensity of shifted bands on PCR-SSCP and positve cell ratio. A discrepancy between p53 protein expression and p53 mutation is observed in primary gastric carcinomas. The reason for this discrepancy are not apparent. However, examination of gastric carcinomas for mutations in other exons may identify a better correlation with protein overexpression. The results obtained in this study suggest that the negative reaction for p53 immunohistochemistry may not necessarily mean no genetic alteration of the p53 locus.

Distribution of S-100 Protein Positive Dendritic Cell and its Correlation with Degree of Malignancy in Gastric Carcinoma.: Tae Jung Jang, Woo Ick Yang, Chan Il Park, In Joon Choi; Korean J Pathol. 1991;25(4):327-337.

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Abstract PDF: The present study was performed in order to investigate the correlation among the number of T zone histiocytes, the clinicopathologic parameters and the patient's survival. The subjects in this study were 131 advanced gastric carcinomas including 86 follow-up cases and 41 early gastric carcinomas. The infiltration of T zone histiocytes into tumor tissues was investigated using the immunohistochemical method with andti s-100 protein, nd the data obtained were evaluated statistically. T zone histiocytes were scattered among the cancer cells and in areas formed clusters within the cancer stroma. These cells were abundantly present in tumor tissues and around lymphoid follicles but were rarely seen in surrounding normal stomach tissue. Analysis of the number of T zone histiocytes showed no correlation between the number of T zone histiocytes and the clinicopathologic features except the degree of lymphocytic infiltration within the advanced and the early gastric carcinomas. Survival of the patients with a marked infiltration of T zone histiocytes in stage III was longer than that with mild infiltration of T zone histiocytes, but there was no statistical significance(P value=0.084). Multivariate regressio analysis revealed that the depth of invasion(P value=0.0074) and the lymphocytic infiltration(P value=0.0152) were the important prognostic factors. The results indicate that good prognosis is expected in cases with less deep invasion and high lymphocytic infiltration, and that the number of T zone histiocytes is in proportio to the degree of lymphocyte infiltration within the tumor, although not directly correlated with the patient's survival.

Expression of nm23 Protein in Human Gastric Carcinoma: correlation between nm23 expression with the development and metastasis of gastric carcinoma.: Jin Hee Sohn, Hye Rym Park, Young Oui Park; Korean J Pathol. 1996;30(6):487-494.

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Abstract PDF: Gene expression of nm23 has been investigated in many kinds of tumors, including breast cancers, colon cancers, hepatocellular carcinomas, papillary carcinomas of the thyroid and malignant melanomas since the nm23 was dislovered by Dr. Steeg as a tumor metastatic suppressor gene. Reduced expression of nm23 gene implicated in high metastatic potential in a variety of malignancies. However, there have been only a few reports on genetic alteration and expression of nm23 in human gastric carcinomas even though gastric carcinoma is a leading malignancy in Korea. In this study, we examined the expression of nm23 protein by immunohistochemistry in advanced and early gastric carcinomas, adenomas, matching normal mucosa to elucidate the role of nm23 in the development, progression and metastasis of human gastric carcinomas. The results are as follows; 1) Nm23 was expressed in 39 cases(69.6%) of 56 advanced gastric carcinomas. Among them, strong positive cases(grade 3) were 26(46.4%) and weak positive cases(grade 2) were 13(23.2%). 2) Nm23 expression was significantly different (P<0.05) depending on the site of the neoplasm. Antral carcinomas showed grade3 positivity in the 22/37 cases(60%), but carcinomas of the body showed negative (grade 1) result in about half(42.1%). 3) Nm23 expression was more intense in the neoplasm than normal mucosa.(67.9%) 4) Nm23 expression was not significantly related to the lymph node metastasis, invasion of lymphatics or veins and depth of invasion. 5) In the well differentiated carcinomas, grade3 were more common(64.0%). But in cases of signet ring cell carcinoma, many cases were negative(50.0%). 6) Nm23 expression rate and intensity was significantly increased from the normal mucosa to the gastric adenomas, early gastric carcinomas and advanced gastric carcinomas.

Clinicopathologic Significance of Lymph Node Micrometastasis in Advanced Gastric Carcinoma.: Youngmee Kwon, Jae Y Ro, Gyeong Hoon Kang; Korean J Pathol. 2000;34(2):125-131.

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Abstract PDF: There have been some controversies on prognostic significance of lymph node (LN) micrometastasis (MM) in advanced gastric carcinomas (AGCs). The present study aimed at 1) determination of prognostic significance of MM, 2) evaluation of the relationship between MM and clinicopathological parameters, and 3) determination of LN group where MMs were frequently found. We studied 70 cases of AGC without LN metastasis on initial examination. The tumors were examined for location, size, depth of invasion, differentiation, histologic type, lymphatic invasion, and c-erbB-2 expression. To evaluate MM, pancytokeratin immunohistochemistry was performed in all LNs from 70 cases of AGCs. Among 2,203 dissected LNs from 70 patients, 37 (1.6%) LNs from 19 (27.1%) patients revealed MM. Micrometastases were seen in only group 1 and 2 LNs: none had group 3 and 4 LN involvement. The gender, age, tumor size, location of tumor, histologic type, differentiation, depth of invasion, lymphatic invasion, and c-erbB-2 expression were not significantly associated with MM status. The survival time of the MM-positive group (mean: 62 months) was significantly shorter than that of the MM-negative group (mean: 72 months) (p=0.046). The findings of this study indicate that the presence of MM in LNs is an important prognostic factor in AGC patients.

Fascin-1 Protein Expression in Gastric Carcinoma.: Seoung Wan Chae, Jin Hee Sohn; Korean J Pathol. 2006;40(2):112-117.

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Abstract PDF: BACKGROUND
Fascin-1 is a globular cross-linking and actin bundling protein that provides mechanical support to cellular protrusions and cell motility. The expression of fascin in epithelial neoplasms has been recently reported, but its exact mechanism in cancer is unknown. The purpose of this study was to assess the expression of fascin and its relationship with the clinicopathologic parameters and the other tumor markers in gastric carcinoma.
METHODS
Immunohistochemical stainings for fascin, c-erbB-2, p53 and Ki-67 labeling index were performed in 62 gastric carcinoma specimens.
RESULTS
Fascin-1 protein was not expressed in the normal gastric glandular epithelial cells. It had an expression in 35.5% of the gastric adenocarcinomas. The fascin-1 expression in carcinoma was slightly increased in the well to moderately differentiated tumors compared with the poorly differentiated tumors. The fascin-1 expression was correlated with the c-erbB-2 protein expression. There was no significant correlation with the clinicopathologic factors such as tumor size, nodal metastasis, pathologic stage, p53 protein expression and Ki-67 labeling index.
CONCLUSIONS
This study reveals the possibility that the fascin-1 protein expression in gastric carcinoma may be closely linked with the c-erbB-2 protein expression. However, further study on fascin-1 and c-erbB-2 protein at the cellular level and their clinical relevance is needed.

Case Report

Early Gastric Carcinoma with Hepatoid Differentiation: Report of a case with histotopographic analysis.: Gyeong Hoon Kang, Chong Jai Kim, Yong Il Kim; Korean J Pathol. 1991;25(6):594-600.

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Abstract PDF: A 56-year-old man received subtotal gastrectomy for an early gastric carcinoma type IIa+IIc with submucosal invasion. The tumor was made up of mixed papillo-tubular adenocarcinoma and solid carcinomatous portion, the latter comprising approximately four-fifths of the total tumor mass. The solid portion was confined within the submucosa and revealed a mixture of trabecular, compact and pelioid patterns of large polyhedra cells, resembling hepatocellular carcinoma of the liver(Edmondson-Steiner grade 2). Sinusoid-like vascular stroma of classical trabecular hepatocellular carcinoma intervened the tumor cell nests but was not associated with endothelial-cell lining. Immunohistochemical stainings with alpha-fetoprotein and alpha1-antitrypsin gave a strong reactivity in those areas of hepatoid differentiation and in the adjacent minute portion of adenocarcinoma. The findings suggest that a portion of gastric carcinoma may transdifferentiate into cells with hepatoid features along the line of endodermal lineage.

Original Articles

Pathologic Classification of the Resected Gastric Carcinoma.: Gu Kang, Hyung Sik Shin, Min Chul Lee, Young Euy Park, Joo Seop Kim, Chul Jae Park, Soo Tong Pai; Korean J Pathol. 1992;26(1):17-27.

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Abstract PDF: A total of 212 cases of gastric carcinoma resected at Kang-Dong Sacred Heart Hospital during the period of 4 years from December 1986 to December 1990 were examined according to Borrmann, Mulligan-Rember, Ming and WHO methods based on histopathological investigations. In Mulligan-Rember (M-R) classification, intestinal cell type (IC) was frequently seen in Borrmann type I and II; pyloro-cardiac gland cell type (PC) in II and III, and mucous cell type (MC) in IV and III. Expanding growth pattern was more frequent in IC, infiltrative growth pattern in MC, and PC showed less infiltrative growth than MC. In gross type, the most expanding growth pattern was seen in Advanced gastric carcinoma type (AGC) I and the next one was in AGC II; the ratio of infiltrative versus expanding type was highest in AGC IV and next in AGC resembling early gastric carcinoma (EGC) and AGC III in order. On WHO classification except squamous type, all the papillary type showed expanding growth and infiltrative growth was frequently seen in signet-ring cell, undifferentiated, tubular and mucinous types in order. Lymphoid stroma was more frequently found in expanding type than infiltrative type. The frequency of angioinvasion of tumor cells observed was high in AGC resembling EGC, AGC II, III, IV, I and EGC in order. In WHO classification excluding squamous type, undifferentiated and signet-ring cell types occurred more frequently under the age of 60 and papillary type were more frequnetly seen over the age of 60. But tubular type had no difference between the two age groups. In Ming's classification, expanding type was more frequently seen than infiltrative type over the age of 60.

Two Patterns of Gastric Carcinoma with Lymphoid Stroma.: Gu Kang, Eun Sil Yu, Yong Il Kim; Korean J Pathol. 1988;22(4):375-382.

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Abstract PDF: Various clinical and pathologic parameters in order to determine the prognosis of gastric carcinoma have been proposed. Among them "carcinoma with lymphoid stroma" has been proven to show good prognosis. But the criteria of lymphoid stroma in this condition remain vague and not clear. A total of 7 cases of gastric carcinoma with heavy lymphoid stromal response out of 947 surgically resected gastric carcinomas was reviwed with histotopographic analysis. They were all advanced carcinoma, Borrmann type I and II. Histologically, the lymphoid stromal response could be divided into three patterns; nodular (3 cases), diffuse (3 cases) and mixed (1 case). The nodular pattern was characterized by massive lymphoid cell infiltration with many follicle formation and little desmoplastic reaction, while the diffuse pattern showed diffuse permeative type of inflammatory cell infiltration with scarce lymphoid follicle formation and mild desmoplasia. Regional lymph node metastasis was found in 2 cases; one in diffused and another one in mixed pattern. The stromal reaction was not directly related with the depth of tumor invasion. We propoose that the term GCLS should be used in the cases of nodular pattern with complete follicle formation of lymphoid stroma.

Expression of Transforming Growth Factor-beta1 and Its Effects on the Extracellular Matrix Formation and Angiogenesis in Gastric Carcinoma.: Young Hee Choi, Young Euy Park; Korean J Pathol. 1998;32(9):647-654.

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Abstract: Malignant cells in culture express elevated levels of transforming growth factor-beta1 (TGF-beta1) mRNA and secrete an abundant amount of the TGF-beta1 protein. An attempt was made to define the role of the TGF-beta1 secreted from tumor cells, as a possible humoral factor which functions in a paracrine manner to stimulate the production of collagen and angiogenesis in gastric carcinoma. The expression of the TGF-beta1 by immunohistochemical stain (n=70) in gastric adenocarcinoma tissues was studied. Angiogenesis was evaluated by immunohistochemical staining of tumor vessels, using polyclonal antibody to factor VIII related antigen and counting the three most active areas of neovascularization. The extracellular matrix was counted as area density by using an image analyzer following Masson-Trichrome staining. The prominent reactivity for TGF-beta1 was associated with invasion depth (r=0.2, p<0.05), increased number of microvessel (r=0.49, p<0.05) and increased area density of extracellular matrix (r=0.36, p<0.05), respectively. In summary, TGF-beta1 may have a role in tumor invasion and metastasis by increased angiogenesis and deposits of extracellular matrix.

Studies of CD44s and CD44v6 Expressions and Correlation with Clinicopathologic Parameters in Gastric Carcinoma.: Zhu Hu Li, Zhen Hua Lim, Ho Jong Jeon; Korean J Pathol. 2003;37(5):320-324.

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Abstract PDF: BACKGROUND
The aim of this study is to elucidate the relationship between the CD44s and CD44v6 expression level and the biological characteristics of a gastric carcinoma.
METHODS
CD44s and CD44v6 expression was investigated in 56 gastric carcinomas, 18 dysplasias, and 22 normal mucosae by immunohischemical staining.
RESULTS
The CD44s and CD44v6 expression rates in gastric carcinomas, dysplasia, and normal mucosae were 80.3% and 83.9%, 72.2% and 77.8%, and 13.6% and 4.5%, respectively. Statistical analysis showed significant difference after comparing a gastric carcinomas and dysplasia to the normal mucosae (p<0.001). The CD44s and CD44v6 expression rates in the cases with invasion to the muscle proper and serosa were 60.7% and 57.1%, and 82.4% and 88.2%, respectively. Both showed a significant statistical difference compared to the expression rates in the cases with invasion to the mucosae and submucosae. The CD44s and CD44v6 expression rates in gastric carcinomas with a lymph node metastasis showed a statistically significant difference compared to those without a lymph node metastasis (p<0.001 and p<0.01, respectively). CD44s and CD44v6 were also expressed in the normal basal cells around gastric carcinomas.
CONCLUSIONS
The CD44s and CD44v6 expression showed a significant relationship with gastric carcinogenesis, toward an aggressive biologic behavior.

Case Report

A Case of Gastric Inverted Hyperplastic Polyp Associated with Gastritis Cystica Profunda and Early Gastric Carcinoma.: Min Sung Choi, So Young Jin, Dong Won Kim, Dong Wha Lee, Sang Mo Park; Korean J Pathol. 2007;41(1):55-58.

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Abstract PDF: A gastric inverted hyperplastic polyp is characterized by downward growth of the hyperplastic mucosal components into the submucosa. Lesions are composed of hyperplastic foveolar-type glands, and sometimes coexist with gastritis cystica profunda (GCP). Adenocarcinoma frequen- tly can coexist, but the relationship is not clear. A 71-year-old male was admitted to hospital because of dyspepsia for one month. He underwent a wedge resection of the stomach, after endoscopic biopsies. The gross finding showed a slightly elevated papillary lesion with central depression. Microscopically, the elevated lesion was composed of hyperplastic fundic glands and foveolar cells, and the central depressed lesion showed a nodular inverted proliferation of normal appearing gastric epithelium and glands in the submucosa. An additional proximal gastrectomy specimen exhibited marked GCP and a minute adenocarcinoma at the proximal margin with p53 protein overexpression.

Original Articles

Alterations of the Mucin Glycoprotein Expression and Their Relationship with the Pathologic Prognostic Factors in Gastric Carcinoma.: Mee Sook Roh, Gi Yeong Huh, Sook Hee Hong; Korean J Pathol. 1999;33(1):15-24.

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Abstract: Alterations of the mucin-type glycoproteins may contribute to changes in cancer cell growth regulation, immune regulation, and cellular adhesion, which in turn may influence the invasive and metastatic capabilities of the cancer. Many of the cancer-associated antigens such as mucin antigens have been identified recently and alterations in the glycosylation of the mucins have been described in the cancer. Immunohistochemical studies of 3 antigens associated with alteration of the mucin glycoprotein (MUC1, MUC2, STn) were done to evaluate their relationship with known pathologic prognostic factors and their usefulness in assessment of the progression of gastric carcinoma in 127 gastric carcinoma tissues. The MUC1 was detected in 57 (44.9%), MUC2 in 76 (59.8%) and STn antigen in 77 (60.6%) out of 127 cases of gastric carcinomas. The expression rate of MUC1 was significantly correlated with depth of tumor invasion, lymph node and distant metastases, and advanced tumor stage (p=0.001). The expression rate of MUC2 was not significantly correlated with pathologic findings and known prognostic factors. The STn antigen was significantly associated with incidence of lymph node metastasis (p=0.02). The coexpression of both MUC1 and MUC2 or MUC1 and STn was more frequent in tumors with deep invasion, lymph node metastasis and advanced tumor stage than one or none expression (p<0.05). These results suggest that the alterations of expression of the mucin proteins, especially MUC1 and carbohydrate antigen (STn) are associated with poor biological behavior of the gastric carcinoma.

Expression of Cellular Oncogenes in Gastric Carcinoma Related with Its Histologic Subtype: Southern blot analysis and immunohistochemistry.: Jin Sook Jeong, In Hoo Kim; Korean J Pathol. 1992;26(6):543-551.

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Abstract PDF: To search biologic characteristics of gastric carcinoma, one of the most common cancer in Korea, the author examined the alterations in DNA level and the expression of Ha-ras gene and c-myc gene in 20 primary tumors. Amplification of c-Ha-ras DNA was detected in 4(40%) of 10 patients who showed histologic subtype of relatively differentiated adenocarcinoma, but rearrangement of c-Ha-ras DNA was absent. Neither augumentation nor deletion of the c-myc DNA was observed. Higher expression of the ras p21 in tumor cells was noted in more differentiated tumor cells rather than poorly differentiated cases. One mucinous carcinoma, two signet ring cell carcinomas and one papillary carcinoma did not disclose expression of p21. The expressions of c-myc oncogene product were variable and were not correspond to the expressions of ras p21. A tendency that poorly differentiated tumor cells had higher expression of c-myc oncogene was suggested.

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