Combined BRCA2 and MAGEC3 expression predict outcome in Advanced Ovarian Cancers

Abstract

AbstractLike BRCA2, MAGEC3 is an ovarian cancer predisposition gene that has been shown to have prognostic significance in ovarian cancer patients. Despite the clinical significance of each individual gene, no studies have been done to assess the clinical significance of their combined expression. We therefore sought to determine the relationship between MAGEC3 and BRCA2 expression in ovarian cancer and their association with patient characteristics and outcomes. Immuno-histochemical staining was quantitated on tumor microarrays of human tumor samples obtained from 357 patients with epithelial ovarian cancer to ascertain BRCA2 expression levels. In conjunction with our previously published MAGEC3 expression data, we observed a weak inverse correlation of MAGEC3 with BRCA2 expression (r= -0.15; p<0.05) in cases with full-length BRCA2. Patients with optimal cytoreduction, loss of MAGEC3, and detectable BRCA2 expression had better overall (median OS: 127.9 vs 65.3 months, p=0.035) and progression-free (median PFS: 85.3 vs 18.8 months, p=0.002) survival compared to patients that were BRCA2 expressors with MAGEC3 normal levels. Our results suggest that combined expression of MAGEC3 and BRCA2 serves as a better predictor of prognosis than each marker alone.Simple SummaryEarly detection of ovarian cancer is a significant clinical challenge, with most women presenting with advanced stages of disease at initial diagnosis. The aim of this study was to evaluate the role of MAGEC3 and BRCA2 in epithelial ovarian cancer progression. We evaluated the effect of MAGEC3 and BRCA2 on the other’s expression. We tested this in humans using immunohistochemical staining of human tumor samples obtained from patients with epithelial ovarian cancer (n = 357). We found a weak inverse correlation between MAGEC3 and BRCA2 expression in epithelial ovarian cancers. Further, our data suggests that the combined expression of MAGEC3 and BRCA2 may be a better predictor of outcomes in patients than the individual markers alone.