Development of Serous Ovarian Cancer is Associated with the Expression of Homologous Recombination Pathway Proteins

To investigate the expressions of key markers in the homologous recombination (HR) pathway and the correlation with clinicopathological parameters in serous ovarian cancer (SOC). We analyzed the protein expression of MRE11, MDC1, ATM, ATR and BRCA1 by immunohistochemistry (IHC) in 97 SOC samples, and correlated with clinical parameters including age, tumor grades, clinical stage, status of menstruation and chemotherapy. Low expression of MRE11 and MDC1 was detected in 14.4 % and 3.1 % of the patient samples, and negative expression of ATM, ATR and BRCA1 was found in 11.3 %, 6.3 % and 29.9 % of the patient samples, respectively. ATR deficiency was significantly associated with menopause (P = 0.025), strong expression of ATM (P = 0.017) and MRE11 (P = 0.040) with pre-menopausal SOC, strong expression of MRE11 (P = 0.016) with low tumor grade, and strong expression of BRCA1 (P = 0.015) with early clinical stage. In addition, low expression of MRE11 was strongly associated with negativity of ATR (P < 0.001) and BRCA1 (P = 0.004) Furthermore, ATR deficiency was associated with low expression of ATM (P = 0.028) and loss expression of BRCA1 (P = 0.009). Our results suggest that reduced expression or loss of proteins in HR pathway is associated with SOC development. Abnormality of MRE11 and BRCA1 are strongly associated with late clinical stage in SOC patients.