Potential Role of KRAS and BRAF in Epithelial Ovarian Cancer

Abstract

KRAS and BRAF are key proto-oncogenes of MAPK/ERK pathway and are essential for cell growth and proliferation. Mutations of these oncogenes are known to have role in pathogenesis of epithelial ovarian carcinoma (EOC). However, limited studies have evaluated the role of KRAS and BRAF protein expression. Hence, this study aimed to explore their role in EOC patients, specifically to correlate KRAS and BRAF protein expression with the histological subtypes and other histopathological prognostic factors. Immunohistochemistry was performed using paraffin-embedded tumor tissue blocks of 55 untreated and histologically confirmed EOC patients and 20 benign ovarian tumors to study KRAS and BRAF protein expression. Data were analyzed using SPSS software. Cytoplasmic expression of both KRAS and BRAF was observed in EOC and benign tumors. KRAS protein expression was significantly higher in serous EOC patients than the mucinous EOC patients (P = 0.016). KRAS expression was also significantly positively correlated with the presence of lymphatic permeation (P = 0.030), while a trend toward significance was found with vascular permeation (P = 0.052). Furthermore, BRAF protein expression was significantly higher in EOC patients than in benign ovarian tumors (P = 0.027). Its expression was significantly higher in patients with moderately/poorly differentiated tumors than well-differentiated tumors (P = 0.008), and in patients having serous EOC than in mucinous EOC (P = 0.001). A trend of higher BRAF expression was also observed in patients with lymphnode metastasis (P = 0.079). KRAS and BRAF proteins have a potential role in EOCs. However, further studies in larger group of patients and follow-up for a longer period are required to identify their role in prognosis.