학술논문
Quantitative imaging of RAD51 expression as a marker of platinum resistance in ovarian cancer
Document Type
article
Author
Hoppe, Michal M; Jaynes, Patrick; Wardyn, Joanna D; Upadhyayula, Sai Srinivas; Tan, Tuan Zea; Lie, Stefanus; Lim, Diana GZ; Pang, Brendan NK; Lim, Sherlly; Yeong, Joe PS; Karnezis, Anthony; Chiu, Derek S; Leung, Samuel; Huntsman, David G; Sedukhina, Anna S; Sato, Ko; Topp, Monique D; Scott, Clare L; Choi, Hyungwon; Patel, Naina R; Brown, Robert; Kaye, Stan B; Pitt, Jason J; Tan, David SP; Jeyasekharan, Anand D
Source
EMBO Molecular Medicine. 13(5)
Subject
Language
Abstract
Early relapse after platinum chemotherapy in epithelial ovarian cancer (EOC) portends poor survival. A-priori identification of platinum resistance is therefore crucial to improve on standard first-line carboplatin-paclitaxel treatment. The DNA repair pathway homologous recombination (HR) repairs platinum-induced damage, and the HR recombinase RAD51 is overexpressed in cancer. We therefore designed a REMARK-compliant study of pre-treatment RAD51 expression in EOC, using fluorescent quantitative immunohistochemistry (qIHC) to overcome challenges in quantitation of protein expression in situ. In a discovery cohort (n = 284), RAD51-High tumours had shorter progression-free and overall survival compared to RAD51-Low cases in univariate and multivariate analyses. The association of RAD51 with relapse/survival was validated in a carboplatin monotherapy SCOTROC4 clinical trial cohort (n = 264) and was predominantly noted in HR-proficient cancers (Myriad HRDscore