BRAF mutation is associated with early stage disease and improved outcome in patients with low-grade serous ovarian cancer. Academic Article uri icon

Overview

abstract

  • BACKGROUND: Low-grade serous (LGS) ovarian cancer is a chemoresistant disease that accounts for 10% of serous ovarian cancers. Prior studies have reported that 28% to 35% of serous borderline (SB)/LGS ovarian tumors harbor a BRAF mutation, suggesting that BRAF inhibitors may be a rational therapeutic approach for this disease. In the current study, the authors sought to determine whether BRAF or KRAS mutation status was associated with disease stage and/or histology in patients with SB and LGS ovarian cancer. METHODS: Genetic profiles were constructed for 75 SB and LGS ovarian tumors to determine BRAF and KRAS mutation status. The incidence and identity of BRAF and KRAS mutations were defined, and the results were correlated with disease stage, response to treatment, and overall survival. RESULTS: Of 75 samples examined, 56 tumors (75%) had SB histology, and 19 tumors (25%) had LGS histology. Fifty-seven percent of tumors harbored either a KRAS mutation (n = 17) or a BRAF mutation (a valine-to-glutamate substitution at residue 600 [V600E]; n = 26). The BRAF V600E mutation was associated significantly with early disease stage (stage I/II; P < .001) and SB histology (P = .002). KRAS mutations were not associated significantly with disease stage or histology. Of the 22 patients (29%) who required chemotherapy, 20 had tumors with wild-type KRAS/BRAF, 2 had KRAS mutant tumors, and none had tumors that harbored a BRAF mutation. All patients with BRAF tumors remained alive at a median follow-up of 3.6 years (range, 1.9-129.3 months). CONCLUSIONS: V600E BRAF mutations were present in 35% of patients who had SB/LGS ovarian cancers. The presence of the BRAF V600E mutation in SB/LGS ovarian cancer was associated with early stage disease and improved prognosis. The authors concluded that patients with SB/LGS ovarian cancer who require systemic therapy are unlikely to have BRAF mutant tumors.

publication date

  • August 28, 2012

Research

keywords

  • Cystadenoma, Serous
  • Early Detection of Cancer
  • Mutation, Missense
  • Ovarian Neoplasms
  • Proto-Oncogene Proteins B-raf

Identity

PubMed Central ID

  • PMC3961140

Scopus Document Identifier

  • 84872930026

Digital Object Identifier (DOI)

  • 10.1002/cncr.27782

PubMed ID

  • 22930283

Additional Document Info

volume

  • 119

issue

  • 3