Journal of Pathology and Translational Medicine

Reviews

Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists: 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; J Pathol Transl Med. 2024;58(3):103-116. Published online April 25, 2024; DOI: https://doi.org/10.4132/jptm.2024.03.15

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Nivolumab plus chemotherapy in the first-line setting has demonstrated clinical efficacy in patients with human epidermal growth factor receptor 2–negative advanced or metastatic gastric cancer, and is currently indicated as a standard treatment. Programmed death-ligand 1 (PD-L1) expression is an important biomarker for predicting response to anti–programmed death 1/PD-L1 agents in several solid tumors, including gastric cancer. In the CheckMate-649 trial, significant clinical improvements were observed in patients with PD-L1 combined positive score (CPS) ≥ 5, determined using the 28-8 pharmDx assay. Accordingly, an accurate interpretation of PD-L1 CPS, especially at a cutoff of 5, is important. The CPS method evaluates both immune and tumor cells and provides a comprehensive assessment of PD-L1 expression in the tumor microenvironment of gastric cancer. However, CPS evaluation has several limitations, one of which is poor interobserver concordance among pathologists. Despite these limitations, clinical indications relying on PD-L1 CPS are increasing. In response, Korean gastrointestinal pathologists held a consensus meeting for the interpretation of PD-L1 CPS in gastric cancer. Eleven pathologists reviewed 20 PD-L1 slides with a CPS cutoff close to 5, stained with the 28-8 pharmDx assay, and determined the consensus scores. The issues observed in discrepant cases were discussed. In this review, we present cases of gastric cancer with consensus PD-L1 CPS. In addition, we briefly touch upon current practices and clinical issues associated with assays used for the assessment of PD-L1 expression in gastric cancer.

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Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIG
F. Lordick, M.E. Mauer, G. Stocker, C.A. Cella, I. Ben-Aharon, G. Piessen, L. Wyrwicz, G. Al-Haidari, T. Fleitas-Kanonnikoff, V. Boige, R. Lordick Obermannová, U.M. Martens, C. Gomez-Martin, P. Thuss-Patience, V. Arrazubi, A. Avallone, K.K. Shiu, P. Artru
Annals of Oncology.2024;[Epub] CrossRef
PD-L1 thresholds predict efficacy of immune checkpoint inhibition in first-line treatment of advanced gastroesophageal adenocarcinoma. A systematic review and meta-analysis of seven phase III randomized trials
V. Formica, C. Morelli, L. Fornaro, S. Riondino, M. Rofei, E. Fontana, E.C. Smyth, M. Roselli, H.-T. Arkenau
ESMO Open.2024; 9(11): 103967. CrossRef

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

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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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Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists
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
Journal of Pathology and Translational Medicine.2024; 58(3): 103. CrossRef
Expression of claudin 18.2 in poorly cohesive carcinoma and its association with clinicopathologic parameters in East Asian patients
Moonsik Kim, Byung Woog Kang, Jihyun Park, Jin Ho Baek, Jong Gwang Kim
Pathology - Research and Practice.2024; 263: 155628. CrossRef
Clinicopathological analysis of claudin 18.2 focusing on intratumoral heterogeneity and survival in patients with metastatic or unresectable gastric cancer
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
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Histopathology of Gastric Cancer
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The Korean Journal of Helicobacter and Upper Gastrointestinal Research.2023; 23(2): 143. CrossRef
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HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation: Soomin Ahn, Ji Won Woo, Kyoungyul Lee, So Yeon Park; J Pathol Transl Med. 2020;54(1):34-44. Published online November 6, 2019; DOI: https://doi.org/10.4132/jptm.2019.11.03

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Abstract PDF

Human epidermal growth factor receptor 2 (HER2) protein overexpression and/or HER2 gene amplification is found in about 20% of invasive breast cancers. It is a sole predictive marker for treatment benefits from HER2 targeted therapy and thus, HER2 testing is a routine practice for newly diagnosed breast cancer in pathology. Currently, HER2 immunohistochemistry (IHC) is used for a screening test, and in situ hybridization is used as a confirmation test for HER2 IHC equivocal cases. Since the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines on HER2 testing was first released in 2007, it has been updated to provide clear instructions for HER2 testing and accurate determination of HER2 status in breast cancer. During HER2 interpretation, some pitfalls such as intratumoral HER2 heterogeneity and increase in chromosome enumeration probe 17 signals may lead to inaccurate assessment of HER2 status. Moreover, HER2 status can be altered after neoadjuvant chemotherapy or during metastatic progression, due to biologic or methodologic issues. This review addresses recent updates of ASCO/CAP guidelines and factors complicating in the interpretation of HER2 status in breast cancers.

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Case Study

Combined Hepatocellular Carcinoma and Neuroendocrine Carcinoma with Ectopic Secretion of Parathyroid Hormone: A Case Report and Review of the Literature: Hyun Jung Kwon, Ji-Won Kim, Haeryoung Kim, YoungRok Choi, Soomin Ahn; J Pathol Transl Med. 2018;52(4):232-237. Published online May 25, 2018; DOI: https://doi.org/10.4132/jptm.2018.05.17

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Abstract PDF

Primary combined hepatocellular carcinoma (HCC) and neuroendocrine carcinoma is a rare entity, and so is hypercalcemia due to ectopic parathyroid hormone (PTH) secretion by tumor. A 44-year old man with hepatitis B virus associated chronic liver disease presented with a hepatic mass. Hemihepatectomy discovered the mass as combined HCC and poorly differentiated cholangiocarcinoma. During adjuvant chemoradiation therapy, he presented with nausea, and multiple systemic metastases were found. Laboratory tests revealed hypercalcemia with markedly elevated PTH and neuron specific enolase. Parathyroid scan showed normal uptake in parathyroid glands, suggestive of ectopic PTH secretion. Subsequently, immunohistochemistry of neuroendocrine marker was performed on the primary lesion, and confirmed the neuroendocrine differentiation in non-HCC component. The patient died 71 days after surgery. This report may suggest the possibility of ectopic PTH secretion by neuroendocrine carcinoma of hepatic origin causing hypercalcemia. Caution for neuroendocrine differentiation should be exercised when diagnosing poorly differentiated HCC.

Citations

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Original Articles

The Clinicopathological and Prognostic Significance of the Gross Classification of Hepatocellular Carcinoma: Yangkyu Lee, Hyunjin Park, Hyejung Lee, Jai Young Cho, Yoo-Seok Yoon, Young-Rok Choi, Ho-Seong Han, Eun Sun Jang, Jin-Wook Kim, Sook-Hyang Jeong, Soomin Ahn, Haeryoung Kim; J Pathol Transl Med. 2018;52(2):85-92. Published online November 24, 2017; DOI: https://doi.org/10.4132/jptm.2017.11.13

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Abstract PDF

Background
We aimed to determine the clinicopathological significance of the gross classification of hepatocellular carcinoma (HCC) according to the Korean Liver Cancer Association (KLCA) guidelines.
Methods
A retrospective analysis was performed on 242 cases of consecutively resected solitary primary HCC between 2003 and 2012 at Seoul National University Bundang Hospital. The gross classification (vaguely nodular [VN], expanding nodular [EN], multinodular confluent [MC], nodular with perinodular extension [NP], and infiltrative [INF]) was reviewed for all cases, and were correlated with various clinicopathological features and the expression status of “stemness”-related (cytokeratin 19 [CK19], epithelial cell adhesion molecule [EpCAM]), and epithelial-mesenchymal transition (EMT)–related (urokinase plasminogen activator receptor [uPAR] and Ezrin) markers.
Results
Significant differences were seen in overall survival (p=.015) and disease-free survival (p = .034) according to the gross classification; INF type showed the worst prognosis while VN and EN types were more favorable. When the gross types were simplified into two groups, type 2 HCCs (MC/NP/INF) were more frequently larger and poorly differentiated, and showed more frequent microvascular and portal venous invasion, intratumoral fibrous stroma and higher pT stages compared to type 1 HCCs (EN/VN) (p<.05, all). CK19, EpCAM, uPAR, and ezrin expression was more frequently seen in type 2 HCCs (p<.05, all). Gross classification was an independent predictor of both overall and disease-free survival by multivariate analysis (overall survival: p=.030; hazard ratio, 4.118; 95% confidence interval, 1.142 to 14.844; disease-free survival: p=.016; hazard ratio, 1.617; 95% confidence interval, 1.092 to 2.394).
Conclusions
The gross classification of HCC had significant prognostic value and type 2 HCCs were associated with clinicopathological features of aggressive behavior, increased expression of “stemness”- and EMT-related markers, and decreased survival.

Citations

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Transformation to Small Cell Lung Cancer of Pulmonary Adenocarcinoma: Clinicopathologic Analysis of Six Cases: Soomin Ahn, Soo Hyun Hwang, Joungho Han, Yoon-La Choi, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn, Woong-Yang Park; J Pathol Transl Med. 2016;50(4):258-263. Published online May 10, 2016; DOI: https://doi.org/10.4132/jptm.2016.04.19

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Abstract PDF

Background
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are considered the first line treatment for a subset of EGFR-mutated non-small cell lung cancer (NSCLC) patients. Although transformation to small cell lung cancer (SCLC) is one of the known mechanisms of resistance to EGFR TKIs, it is not certain whether transformation to SCLC is exclusively found as a mechanism of TKI resistance in EGFR-mutant tumors.
Methods
We identified six patients with primary lung adenocarcinoma that showed transformation to SCLC on second biopsy (n = 401) during a 6-year period. Clinicopathologic information was analyzed and EGFR mutation results were compared between initial and second biopsy samples.
Results
Six patients showed transformation from adenocarcinoma to SCLC, of which four were pure SCLCs and two were combined adenocarcinoma and SCLCs. Clinically, four cases were EGFR-mutant tumors from non-smoking females who underwent TKI treatment, and the EGFR mutation was retained in the transformed SCLC tumors. The remaining two adenocarcinomas were EGFR wild-type, and one of these patients received EGFR TKI treatment.
Conclusions
NSCLC can acquire a neuroendocrine phenotype with or without EGFR TKI treatment.

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Case Study

Pulmonary Arteriovenous Fistula: Clinical and Histologic Spectrum of Four Cases: Soomin Ahn, Joungho Han, Hong Kwan Kim, Tae Sung Kim; J Pathol Transl Med. 2016;50(5):390-393. Published online May 9, 2016; DOI: https://doi.org/10.4132/jptm.2016.04.18

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Abstract PDF

Pulmonary arteriovenous fistula (PAVF) is abnormally dilated vessels that provide a right-to-left shunt between pulmonary artery and pulmonary vein and is clinically divided into simple and complex type. Here, we report four cases of surgically resected sporadic PAVFs presenting various clinical and histologic spectrums. Cases 1 (a 57-old-female) and 2 (a 54-old-female) presented as incidentally identified single aneurysmal fistulas and the lesions were surgically removed without complication. On the other hand, case 3 (an 11-old-male) showed diffuse dilated vascular sacs involving both lungs and caused severe hemodynamic and pulmonary dysfunction. Embolization and surgical resection of the main lesion failed to relieve the symptoms. Case 4 (a 36-old-male) had a localized multiloculated cyst clinically mimicking congenital cystic adenomatoid malformation. Microscopically, the lesion consisted of dilated thick vessels, consistent with the diagnosis of fistulous arteriovenous malformation/hemangioma.

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Brief Case Report

A Rare Case of Pulmonary Arteriovenous Hemangioma Presenting as a Peribronchial Mass: Soomin Ahn, Sejin Jung, Jong Ho Cho, Tae Sung Kim, Joungho Han; J Pathol Transl Med. 2016;50(3):243-245. Published online November 17, 2015; DOI: https://doi.org/10.4132/jptm.2015.10.15

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PDF

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Incidental discovery of a large complicated arteriovenous haemangioma
Alberto Anthony Goizueta, Peter Libbey, Anthony Moulton, Rabih El-Bizri
BMJ Case Reports.2017; : bcr-2016-218759. CrossRef
Pulmonary Arteriovenous Fistula: Clinical and Histologic Spectrum of Four Cases
Soomin Ahn, Joungho Han, Hong Kwan Kim, Tae Sung Kim
Journal of Pathology and Translational Medicine.2016; 50(5): 390. CrossRef

Original Articles

Pleural Mesothelioma: An Institutional Experience of 66 Cases: Soomin Ahn, In Ho Choi, Joungho Han, Jhingook Kim, Myung-Ju Ahn; Korean J Pathol. 2014;48(2):91-99. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.91

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Abstract PDF

Background

Malignant mesothelioma of the pleura is an aggressive tumor known to be associated with asbestos. Histological diagnosis of mesothelioma is challenging and is usually aided by immunohistochemical markers.

Methods

During an 18-year period (1995-2012), 66 patients with pleural mesothelioma were diagnosed at the Samsung Medical Center in Seoul. We reviewed hematoxylin and eosin and immunohistochemical slides of pleural mesothelioma and evaluated their pathological and clinical features.

Results

The male-to-female ratio was 1.75:1, and age of patients ranged from 28 to 80 years with an average age of 56.84 years. Twenty-two out of 66 patients underwent curative pneumonectomy. Follow-up data was available in 60 patients (90.9%), and 50 of them (83.3%) died from the disease. The average overall survival was 15.39 months. Histologically, the epithelioid type was the most common, followed by the sarcomatoid and the biphasic types. Epidemiologic information was not available in most cases, and only one patient was confirmed to have a history of asbestos exposure.

Conclusions

Malignant mesothelioma of the pleura is a fatal tumor, and the therapeutic benefit of pneumonectomy remains unproven. The combination of calretinin, Wilms tumor 1, HMBE-1, and thyroid transcription factor-1 may provide high diagnostic accuracy in diagnosing mesothelioma.

Citations

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Is the pathology related to the amount of pleural thickening measured by thorax CT?
özgür katrancıoğlu, Tuba Sahinoglu, Kayhan Karakus, Ozan Kandemir, Semiha Urvay, Esra Aydın Karakaya, Nurkay Katrancioglu
Cumhuriyet Medical Journal.2018; 40(2): 157. CrossRef

Comparison of Three BRAF Mutation Tests in Formalin-Fixed Paraffin Embedded Clinical Samples: Soomin Ahn, Jeeyun Lee, Ji-Youn Sung, So Young Kang, Sang Yun Ha, Kee-Taek Jang, Yoon-La Choi, Jung-Sun Kim, Young Lyun Oh, Kyoung-Mee Kim; Korean J Pathol. 2013;47(4):348-354. Published online August 26, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.4.348

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Abstract PDF

Background

Recently, BRAF inhibitors showed dramatic treatment outcomes in BRAF V600 mutant melanoma. Therefore, the accuracy of BRAF mutation test is critical.

Methods

BRAF mutations were tested by dual-priming oligonucleotide-polymerase chain reaction (DPO-PCR), direct sequencing and subsequently retested with a real-time PCR assay, cobas 4800 V600 mutation test. In total, 64 tumors including 34 malignant melanomas and 16 papillary thyroid carcinomas were analyzed. DNA was extracted from formalin-fixed paraffin embedded tissue samples and the results of cobas test were directly compared with those of DPO-PCR and direct sequencing.

Results

BRAF mutations were found in 23 of 64 (35.9%) tumors. There was 9.4% discordance among 3 methods. Out of 6 discordant cases, 4 cases were melanomas; 3 cases were BRAF V600E detected only by cobas test, but were not detected by DPO-PCR and direct sequencing. One melanoma patient with BRAF mutation detected only by cobas test has been on vemurafenib treatment for 6 months and showed a dramatic response to vemurafenib. DPO-PCR failed to detect V600K mutation in one case identified by both direct sequencing and cobas test.

Conclusions

In direct comparison of the currently available DPO-PCR, direct sequencing and real-time cobas test for BRAF mutation, real-time PCR assay is the most sensitive method.

Citations

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Comparison of Five Different Assays for the Detection of BRAF Mutations in Formalin-Fixed Paraffin Embedded Tissues of Patients with Metastatic Melanoma
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Transformation to Small Cell Lung Cancer of Pulmonary Adenocarcinoma: Clinicopathologic Analysis of Six Cases
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Immunohistochemistry with the anti-BRAF V600E (VE1) antibody: impact of pre-analytical conditions and concordance with DNA sequencing in colorectal and papillary thyroid carcinoma
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Prognostic Significance of BCL9 Expression in Hepatocellular Carcinoma: Jiyeon Hyeon, Soomin Ahn, Jae Jun Lee, Dae Hyun Song, Cheol-Keun Park; Korean J Pathol. 2013;47(2):130-136. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.130

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Abstract PDF

Background

BCL9 enhances β-catenin-mediated transcriptional activity regardless of the mutational status of the Wnt signaling components and increases the cell proliferation, migration, invasion, and metastatic potential of tumor cells. The goal of this study was to elucidate the prognostic significance of BCL9 protein expression in hepatocellular carcinoma (HCC) patients.

Methods

We evaluated BCL9 protein expression by immunohistochemistry in tumor tissue from 288 primary HCC patients who underwent curative hepatectomy. The impact of BCL9 expression on the survival of the patients was analyzed. The median follow-up period was 97.1 months.

Results

Nuclear BCL9 protein expression was observed in 74 (25.7%) of the 288 HCCs. BCL9 expression was significantly associated with younger age (p=0.038), higher Edmondson grade (p=0.001), microvascular invasion (p=0.013), and intrahepatic metastasis (p=0.017). Based on univariate analyses, BCL9 expression showed an unfavorable influence on both disease-free survival (DFS, p=0.012) and disease-specific survival (DSS, p=0.032). Multivariate analyses revealed that higher Barcelona Clinic Liver Cancer stage was an independent predictor of both shorter DFS (p<0.001) and shorter DSS (p<0.001). BCL9 expression tended to be an independent predictor of shorter DFS (p=0.078).

Conclusions

BCL9 protein expression might be a marker of shorter DFS in HCC patients after curative hepatectomy.

Citations

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Eman Abd El Razek Abbas, Ahmed Barakat Barakat, Mohamed Hassany, Samar Samir Youssef
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Molecular Targets and Signaling Pathways of microRNA-122 in Hepatocellular Carcinoma
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Wnt/β-Catenin Signalling and Its Cofactor BCL9L Have an Oncogenic Effect in Bladder Cancer Cells
Roland Kotolloshi, Mieczyslaw Gajda, Marc-Oliver Grimm, Daniel Steinbach
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Zhuang Wei, Mei Feng, Zhongen Wu, Shuru Shen, Di Zhu
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Ivana Samaržija
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Nuclear Expression of Pygo2 Correlates with Poorly Differentiated State Involving c-Myc, PCNA and Bcl9 in Myanmar Hepatocellular Carcinoma
Myo Win Htun, Yasuaki Shibata, Kyaw Soe, Takehiko Koji
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Wnt status-dependent oncogenic role of BCL9 and BCL9L in hepatocellular carcinoma
Nicole Huge, Maria Sandbothe, Anna K. Schröder, Amelie Stalke, Marlies Eilers, Vera Schäffer, Brigitte Schlegelberger, Thomas Illig, Beate Vajen, Britta Skawran
Hepatology International.2020; 14(3): 373. CrossRef
Structure and function of Pygo in organ development dependent and independent Wnt signalling
Yan Shi, Xiushan Wu, Shuoji Zhu, Huanlei Huang, Jian Zhuang, Haiyun Yuan, Wuzhou Yuan, Ping Zhu
Biochemical Society Transactions.2020; 48(4): 1781. CrossRef
BCL9/BCL9L in hepatocellular carcinoma: will it or Wnt it be the next therapeutic target?
Akshata Moghe, Satdarshan P. Monga
Hepatology International.2020; 14(4): 460. CrossRef
Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer
David M. Gay, Rachel A. Ridgway, Miryam Müller, Michael C. Hodder, Ann Hedley, William Clark, Joshua D. Leach, Rene Jackstadt, Colin Nixon, David J. Huels, Andrew D. Campbell, Thomas G. Bird, Owen J. Sansom
Nature Communications.2019;[Epub] CrossRef
Immunohistochemical Mapping of Bcl9 Using Two Antibodies that Recognize Different Epitopes Is Useful to Characterize Juvenile Development of Hepatocellular Carcinoma in Myanmar
Myat Thu Soe, Yasuaki Shibata, Myo Win Htun, Kuniko Abe, Kyaw Soe, Nay Win Than, Thann Lwin, Myat Phone Kyaw, Takehiko Koji
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Jing Wang, Mingjun Zheng, Liancheng Zhu, Lu Deng, Xiao Li, Linging Gao, Caixia Wang, Huimin Wang, Juanjuan Liu, Bei Lin
Cancer Cell International.2019;[Epub] CrossRef
SOX7 Suppresses Wnt Signaling by Disrupting β-Catenin/BCL9 Interaction
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Hypoxia activates Wnt/β-catenin signaling by regulating the expression of BCL9 in human hepatocellular carcinoma
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CHD1L Is a Marker for Poor Prognosis of Hepatocellular Carcinoma after Surgical Resection: Jiyeon Hyeon, Soomin Ahn, Cheol-Keun Park; Korean J Pathol. 2013;47(1):9-15. Published online February 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.9

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Abstract PDF

Background

The gene for chromodomain helicase/ATPase DNA binding protein 1-like (CHD1L) was recently identified as a target oncogene within the 1q21 amplicon, which occurs in 46% to 86% of primary hepatocellular carcinoma (HCC) cases. However, the prognostic significance of CHD1L in HCC remains uncertain. In this study, we investigated the roles of CHD1L in the prognosis of HCC.

Methods

We investigated the expressions of CHD1L in tumor tissue microarrays of 281 primary HCC patients who underwent surgical resection using immunohistochemistry. Prognostic factors of HCC were examined by univariate and multivariate analyses. The median follow-up period was 75.6 months.

Results

CHD1L expression was observed in 48 of the 281 HCCs (17.1%). CHD1L expression was associated with a younger age (p=0.033), higher Edmondson grade (p=0.019), microvascular invasion (p<0.001), major portal vein invasion (p=0.037), higher American Joint Committee on Cancer T stage (p=0.001), lower albumin level (p=0.047), and higher α-fetoprotein level (p=0.002). Multivariate analyses revealed that CHD1L expression (p=0.027), Edmondson grade III (p=0.034), and higher Barcelona Clinic Liver Cancer stage (p<0.001) were independent predictors of shorter disease-free survival.

Conclusions

CHD1L expression might be a prognostic marker of shorter disease-free survival in HCC patients after surgical resection.

Citations

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Clinicopathological Analysis of 21 Thymic Neuroendocrine Tumors: Soomin Ahn, Jae Jun Lee, Sang Yun Ha, Chang Ohk Sung, Jhingook Kim, Joungho Han; Korean J Pathol. 2012;46(3):221-225. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.221

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Abstract PDF

Background

Thymic neuroendocrine carcinomas (NECs) are uncommon, for which there is no established information available because of a limited number of epidemiological study in Asia.

Methods

We reviewed 21 cases of surgically resected thymic NECs, and evaluated their pathological and clinical features.

Results

It showed male predominance (male/female ratio, 15/6) with wide age range from 20 to 72 years (mean age, 49 years). All 21 cases were divided into two types according to the World Health Organization criteria: atypical carcinoid (n=18) and large cell NEC (n=3). Three cases of atypical carcinoid (AC) were associated with ectopic Cushing's syndrome. All the patients (3/3) with large cell NEC (3/3) and 16.7% (3/18) of those with AC died of tumor progression. Common sites of metastasis included lung, lymph node, brain, lumbar spine, mediastinum, bone, and liver.

Conclusions

In conclusion, thymic neuroendocrine tumors carry a poor prognosis. Regarding the tumor classification, our results showed that a vast majority of carcinoids in the thymus correspond to ACs. In addition, our results also indicate that typical carcinoid is a very rare entity. Some cases of AC exhibited a large size, solid pattern and they showed aggressive clinical behavior, which highlights the spectrum of histologic appearances of thymic NECs.

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