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BRCA1 and BRCA2 mRNA-expression prove to be of clinical impact in ovarian cancer.

Authors :
Tsibulak, Irina
Wieser, Verena
Degasper, Christine
Shivalingaiah, Giridhar
Wenzel, Sören
Sprung, Susanne
Lax, Sigurd F.
Marth, Christian
Fiegl, Heidelinde
Zeimet, Alain G.
Source :
British Journal of Cancer; Sep2018, Vol. 119 Issue 6, p683-692, 10p, 3 Charts, 3 Graphs
Publication Year :
2018

Abstract

<bold>Background: </bold>Mutations in BRCA1 and BRCA2 are associated with better survival in ovarian cancer (OC) patients due to a better response to platinum-based chemotherapy. However, the impact of the BRCA1/2 mRNA-expression is not well characterized in OC.<bold>Patients and Methods: </bold>We investigated BRCA1/2 mRNA-expression in 12 non-neoplastic fallopian tubes and 201 epithelial OCs in relation to their clinical characteristics.<bold>Results: </bold>We found higher BRCA1/2 mRNA-expression in OCs compared to controls (P = 0.011, P < 0.001, respectively). BRCA1 mutated OCs exhibited lower BRCA1 (P = 0.014) but higher BRCA2 mRNA-expression (P = 0.001). Low BRCA1-expression was associated with favorable overall survival (OS) (P = 0.012) and low BRCA2-expression with better progression-free survival (PFS) and OS (P = 0.004, P = 0.001, respectively). A subgroup-analysis showed that this effect was confined only to the BRCA1-wildtype cancers. Cox-regression confirmed the prognostic significance of BRCA1-expression for OS (P = 0.028). Independency of the prognostic value of BRCA2-expression for PFS (P = 0.045) and OS (P = 0.015) was restricted to high-grade serous OCs. Fully platinum-sensitivity was characterized by lower BRCA1/2 mRNA-expression in BRCA1-wildtype cancers in comparison to platinum-refractory OC.<bold>Conclusion: </bold>Our findings may reflect higher platinum-sensitivity due to reduced capacity of DNA damage repair in tissues with low BRCA1/2-expression. In this context, especially in BRCA-wildtype cancers both parameters could also be potential predictors for PARP-sensitivity. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00070920
Volume :
119
Issue :
6
Database :
Complementary Index
Journal :
British Journal of Cancer
Publication Type :
Academic Journal
Accession number :
132187544
Full Text :
https://doi.org/10.1038/s41416-018-0217-4