KRAS mutation of extraovarian implants of serous borderline tumor: prognostic indicator for adverse clinical outcome

In contrast to non-invasive extraovarian implants, invasive implants of ovarian serous borderline tumor/atypical proliferative serous tumor are associated with adverse outcome and have been reclassified as low-grade serous carcinoma. Mutations of KRAS and/or BRAF have been reported in up to 50% of serous borderline tumor/atypical proliferative serous tumor. We investigated KRAS and BRAF mutation frequencies in the two types of implants of serous borderline tumor/atypical proliferative serous tumor in correlation with clinical outcome. Forty-two implants of serous borderline tumor from 39 patients were included (invasive implants/low-grade serous carcinoma, n=20; non-invasive implants, n=22). KRAS mutation was found in 12 of 20 invasive implants (60%) and 3 of 22 non-invasive implants (14%). BRAF V600E mutation was found in 1 of 22 non-invasive implants (5%) and none in invasive implants (0%). Invasive implants were more frequently associated with higher stage disease. Nine of 14 patients (64%) with KRAS mutation were found to have stage IIIC disease, while 5 of 24 patients (20%) without the mutation had stage IIIC disease. Patients with invasive implants had higher recurrence rate compared to those with non-invasive implants (60 vs 14 %, P=0.0003, log-rank test) and worse disease-specific survival (P=0.0008, log-rank test). Regardless of the histological subtypes, patients with KRAS mutation positive implants had significantly higher recurrence rate than those without the mutation (71 vs 21%, P=0.0021, log-rank test) and an unfavorable disease-specific survival (P=0.0104, log-rank test). In conclusion, compared to those with non-invasive implants, patients with invasive implants present with higher stage of the disease, higher recurrence rate and worse survival. KRAS mutation, but not BRAF V600E mutation, is significantly associated with invasive implants of serous borderline tumor. Regardless of the histological subtypes of the implants, KRAS mutation is a significant prognostic indicator for high risk of tumor recurrence and worse disease-specific survival.