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Loss of BAP1 Expression Occurs Frequently in Intrahepatic Cholangiocarcinoma
- Source :
- Medicine
- Publication Year :
- 2016
- Publisher :
- Wolters Kluwer Health, 2016.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 15365964 and 00257974
- Volume :
- 95
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Medicine
- Accession number :
- edsair.doi.dedup.....f679af2273203884693e35368019f4df