BRAF Mutation Is Rare in Advanced-Stage Low-Grade Ovarian Serous Carcinomas

Abstract

Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study , we found that advanced-stage , low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF , and KRAS. TP53 mutations were not detected in any serous borderline tumors (n ‫؍‬ 30) or low-grade serous carcinomas (n ‫؍‬ 43) but were found in 73% of high-grade serous carcinomas (n ‫؍‬ 18). BRAF (n ‫؍‬ 9) or KRAS (n ‫؍‬ 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II , and 2 stage I) , only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas , which contrasts with previous findings , suggests that aggressive , low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition , advanced-stage , low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However , further investigation is needed.

The diagnostic utility of TP53 and CDKN2A to distinguish ovarian high-grade serous carcinoma from low-grade serous ovarian tumors

“…4 Although some reports have shown BRAF mutations in about 30% of cases, 4,30 our inability to detect BRAF V600E mutation in a single low-grade serous carcinomas is in line with a previous report in which Wong et al 31 assessed 43 advanced stage low-grade serous carcinomas. KRAS mutations were detected in 19% of cases, whereas BRAF mutations were found in only 2% of cases, which is very similar to our results.…”

New Strategies in the Treatment of Ovarian Cancer: Current Clinical Perspectives and Future Potential

“…34). Although the incidence of BRAF mutations appears lower in recent reports (35), the Ras/MEK/ERK pathway is still an attractive therapeutic target in this notoriously difficult disease. A phase II trial of the MEK1/2 inhibitor selumetinib (AZD6244) in 52 patients with recurrent LGSOC has shown promising results (36): The overall response rate was 15.4%, disease stabilization 65%, and median PFS 11 months.…”

BRAF mutational analysis in ovarian tumors: recent perspectives

“…Most studies of ovarian LGSC reported a low frequency of BRAF mutations (Table 4). 11,27,45,[55][56][57][58][59] In one study of the implants that accompany ovarian SBTs, only six (13%) of 45 patients had BRAF mutations in SBTs with noninvasive peritoneal implants, and none of the patients had BRAF mutations in SBTs with invasive implants. 43 Heublein et al 44 detected BRAF mutations in only noninvasive implants associated with ovarian SBTs.…”

“…Validation of BRAF mutations as a potential prognostic marker in a large cohort of patients with ovarian SBTs or LGSC is necessary to determine the clinical significance of BRAF status in the management of patients with this disease. Once the BRAF mutation has been confirmed as a protective factor against the progression of ovarian SBTs and early-stage LGSC into more aggressive disease, 11,23,43,58 clinicians will be able to use the BRAF status of surgically resected ovarian SBTs to predict the risk of recurrence. Moreover, for progressive SBT/LGSC with BRAF V600E mutation, treatment with BRAF V600E specific inhibitor could be an alternative regimen.…”