Cover Image

Loss of BAP1 expression occurs frequently in intrahepatic cholangiocarcinoma

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Andrici, Juliana (Author) , Goeppert, Benjamin (Author) , Sioson, Loretta (Author) , Clarkson, Adele (Author) , Renner, Marcus (Author) , Stenzinger, Albrecht (Author) , Tayao, Michael (Author) , Watson, Nicole (Author) , Farzin, Mahtab (Author) , Toon, Christopher W. (Author) , Smith, Ross C. (Author) , Mittal, Anubhav (Author) , Samra, Jaswinder S. (Author) , Hugh, Thomas J. (Author) , Chou, Angela (Author) , Lawlor, Rita T. (Author) , Weichert, Wilko (Author) , Schirmacher, Peter (Author) , Sperandio, Nicola (Author) , Ruzzenente, Andrea (Author) , Scarpa, Aldo (Author) , Gill, Anthony J. (Author)
Format: Article (Journal)
Language:English
Published: January 2016
In: Medicine
Year: 2016, Volume: 95, Issue: 2, Pages: e2491
ISSN:1536-5964
DOI:10.1097/MD.0000000000002491
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1097/MD.0000000000002491
Verlag, lizenzpflichtig, Volltext: https://journals.lww.com/md-journal/Fulltext/2016/01120/Loss_of_BAP1_Expression_Occurs_Frequently_in.67.aspx
Get full text
Author Notes:Andrici, Juliana MBBS, MPhil, Goeppert, Benjamin MD, Sioson, Loretta BSc, Clarkson, Adele BSc, Renner, Marcus PhD, Stenzinger, Albrecht MD, Tayao, Michael BSc, Watson, Nicole, Farzin, Mahtab MD, FRCPA, Toon, Christopher W. MBBS, FRCPA, Smith, Ross C. MD, FRACS, Mittal, Anubhav MBChB, FRACS, PhD, Samra, Jaswinder S. DPhil, FRACS, Hugh, Thomas J. MD, FRACS, Chou, Angela MBBS, FRCPA, Lawlor, Rita T. MSc, Weichert, Wilko MD, Schirmacher, Peter MD, Sperandio, Nicola BA, Ruzzenente, Andrea MD, PhD, Scarpa, Aldo MD, Gill, and Anthony J. MD, FRCPA
Description
Summary: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.
Item Description:Gesehen am 18.08.2020
Physical Description:Online Resource
ISSN:1536-5964
DOI:10.1097/MD.0000000000002491

Similar Items