title: The Prognostic Value of BRCA1 and PARP Expression in Epithelial Ovarian Carcinoma: Immunohistochemical Detection.
abstract: BRCA1/2 mutation status in epithelial ovarian cancer (EOC) presently relies on genetic testing which is resource consuming. Immunohistochemistry is cheap, fairly reproducible, and may identify gene product alterations due to both germline and somatic mutations and other defects along the BRCA gene pathway (BRCAness phenomenon), which is important when treatment with poly (adenosine-diphosphate-ribose) polymerase (PARP) inhibitors is considered. The aim of this study was to investigate immunohistochemical detection of BRCA1 and PARP expression in EOC and their possible prognostic relevance. Tumor tissue from 170 patients with EOC was stained immunohistochemically with BRCA1 and PARP antibodies. Semiquantitative analyses were performed to determine loss of, equivocal, and retained BRCA1 and high versus low PARP protein expression. These parameters were analyzed for relation with patient and clinicopathologic characteristics and overall survival. BRCA1 expression was reduced in 21.2 % of the tumors and 36.5% showed high PARP expression. No correlation between the 2 parameters or between PARP and clinicopathologic features was found. Overall survival was significantly increased in the BRCA1-reduced and equivocal groups [median survival 2.4 y (95% CI, 1.6-6.6) and 4.9 y (95 % CI, 2.3-6.7) vs. 1.5 y (95% CI, 1.3-1.9); P=0.0002]. Multivariate analysis confirmed these findings; hazard ratio=0.53 (95% CI, 0.34-0.81; P=0.0037; loss of BRCA1 expression). In conclusion, immunohistochemical BRCA1 expression in EOC holds considerable prognostic information, whereas PARP expression did not influence the outcome. The results call for validation in prospective trials.
authors.affiliation: Departments of Oncology (M.H., A.J., H.K., K.D.S.) Pathology (M.W.), Vejle Hospital, Vejle Department of Gynaecology and Obstetrics (M.H., E.S.A.), Aalborg University Hospital, Aalborg Institute of Regional Health Research (M.H., M.W., A.J., K.D.S.), University of Southern Denmark, Odense Department of Gynaecology and Obstetrics (M.H.), Viborg Hospital, Viborg, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Hjortkjær
authors.forename: Marianne
authors.initials: M
authors.lastname: Waldstrøm
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen
authors.forename: Hanne
authors.initials: H
authors.lastname: Kanstrup
authors.forename: Erik
authors.initials: E
authors.lastname: Søgaard-Andersen
authors.forename: Karina
authors.initials: K
authors.lastname: Dahl Steffensen
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D044767:Ubiquitin-Protein Ligases / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases; D011065:Poly(ADP-ribose) Polymerases