Loss of BAP1 Expression Occurs Frequently in Intrahepatic Cholangiocarcinoma
| العنوان: | Loss of BAP1 Expression Occurs Frequently in Intrahepatic Cholangiocarcinoma |
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| المؤلفون: | Mahtab Farzin, Nicole Watson, Jaswinder S. Samra, Christopher W. Toon, Wilko Weichert, Benjamin Goeppert, Loretta Sioson, Anubhav Mittal, Anthony J. Gill, Nicola Sperandio, Michael Tayao, Angela Chou, Aldo Scarpa, Andrea Ruzzenente, Marcus Renner, Ross C. Smith, Adele Clarkson, Peter Schirmacher, Juliana Andrici, Rita T. Lawlor, Thomas J. Hugh, Albrecht Stenzinger |
| المصدر: | Medicine |
| بيانات النشر: | Wolters Kluwer Health, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, BRCA1-associated protein 1 (BAP1), deubiquitinating enzyme, tumor suppressor gene, Adult, Male, Pathology, medicine.medical_specialty, Tumor suppressor gene, Lymphovascular invasion, Observational Study, Gastroenterology, Cholangiocarcinoma, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Germany, medicine, Biomarkers, Tumor, Humans, tumor suppressor gene, deubiquitinating enzyme, Intrahepatic Cholangiocarcinoma, Aged, Retrospective Studies, Aged, 80 and over, BAP1, business.industry, Tumor Suppressor Proteins, Hazard ratio, Retrospective cohort study, General Medicine, Odds ratio, Middle Aged, BRCA1-associated protein 1 (BAP1), 030104 developmental biology, Bile Ducts, Intrahepatic, Phenotype, Bile Duct Neoplasms, Italy, 030220 oncology & carcinogenesis, Immunohistochemistry, Female, New South Wales, business, Ubiquitin Thiolesterase, Research Article |
| الوصف: | BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme that functions as a tumor suppressor gene. Double hit BAP1 inactivation has been reported in a range of tumor types, including intrahepatic cholangiocarcinoma (ICC), sometimes in association with germline mutation. We performed immunohistochemistry for BAP1 on a well-characterized cohort of 211 ICC patients undergoing surgical resection with curative intent at 3 institutions based in 3 different countries. The median age at diagnosis was 65 years (range, 36.5–86) and 108 (51%) were men. Negative staining for BAP1 (defined as completely absent nuclear staining in the presence of positive internal controls in nonneoplastic cells) occurred in 55 ICCs (26%). BAP1 loss predicted a strong trend toward improved median survival of 40.80 months (95% CI, 28.14–53.46) versus 24.87 months (95% CI, 18.73–31.01), P = 0.059). In a multivariate model including age, sex, BAP1 status, tumor stage, tumor grade, lymphovascular invasion, and tumor size, female sex was associated with improved survival (hazard ratio [HR] 0.54; 95% CI, 0.34–0.85), while advanced tumor stage and lymphovascular invasion (HR 1.89; 95% CI, 1.09–3.28) correlated with decreased survival. In a multivariate analysis, high grade tumors were associated with BAP1 loss (odds ratio [OR] 3.32; 95% CI, 1.29–8.55), while lymphatic invasion was inversely associated with BAP1 loss (OR 0.36; 95% CI, 0.13–0.99). In conclusion, we observed a trend toward improved prognosis in ICC associated with absent expression of BAP1 and an association of BAP1 loss with higher histological grade and absent lymphatic invasion. Female sex was associated with improved survival while advanced tumor stage and lymphatic invasion were associated with decreased survival. |
| اللغة: | English |
| تدمد: | 1536-5964 0025-7974 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f679af2273203884693e35368019f4dfTest http://europepmc.org/articles/PMC4718285Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f679af2273203884693e35368019f4df |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15365964 00257974 |
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