The prognostic value of BRCA1 and PARP expression in epithelial ovarian carcinoma – immunohistochemical detection
| Autor: | Karina Dahl Steffensen, Mette Hjortkjær, Marianne Waldstrøm, Erik Søgaard-Andersen, Anders Jakobsen, Hanne Kanstrup |
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| Předmět: |
0301 basic medicine
Oncology Adult medicine.medical_specialty endocrine system diseases Somatic cell Ubiquitin-Protein Ligases Kaplan-Meier Estimate Carcinoma Ovarian Epithelial medicine.disease_cause Germline Pathology and Forensic Medicine Gene product 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Biomarkers Tumor Humans Neoplasms Glandular and Epithelial Aged Proportional Hazards Models Retrospective Studies Ovarian Neoplasms Mutation biology Proportional hazards model business.industry Hazard ratio Obstetrics and Gynecology Middle Aged Prognosis Immunohistochemistry 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Female Antibody Poly(ADP-ribose) Polymerases business |
| Zdroj: | University of Southern Denmark Hjortkjær, M, Waldstrøm, M, Kanstrup, H, Søgaard-Andersen, E, Jakobsen, A & Dahl Steffensen, K 2015, ' The prognostic value of BRCA1 and PARP expression in epithelial ovarian carcinoma – immunohistochemical detection ', Årsmøde, Dansk Gynækologisk Cancer Gruppe, 2015, Vejle, Denmark, 19/03/2015-19/03/2015 . Hjortkjær, M, Waldstrøm, M, Jakobsen, A, Kanstrup, H, Søgaard-Andersen, E & Dahl Steffensen, K 2016, ' The prognostic value of BRCA1 and PARP expression in epithelial ovarian carcinoma – immunohistochemical detection ', Annual Meeting of the Danish Pathology Society (DPAS) 2016, København, Denmark, 10/03/2016-12/03/2016 . Hjortkjær, M, Waldstrøm, M, Jakobsen, A, Kanstrup, H, Søgaard-Andersen, E & Dahl Steffensen, K 2017, ' The Prognostic Value of BRCA1 and PARP Expression in Epithelial Ovarian Carcinoma : Immunohistochemical Detection ', International Journal of Gynecological Pathology, vol. 36, no. 2, pp. 180-189 . https://doi.org/10.1097/PGP.0000000000000310 Hjortkjær, M, Waldstrøm, M, Kanstrup, H, Søgaard-Andersen, E, Jakobsen, A & Dahl Steffensen, K 2014, ' The prognostic value of BRCA1 and PARP expression in epithelial ovarian carcinoma – immunohistochemical detection ', 15th biennial meeting of the International Gynecologic Cancer Society., Melbourne, Australia, 08/11/2014-11/12/2014 . |
| DOI: | 10.1097/PGP.0000000000000310 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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