BRAF mutation is associated with early stage disease and improved outcome in patients with low-grade serous ovarian cancer
- PMID: 22930283
- PMCID: PMC3961140
- DOI: 10.1002/cncr.27782
BRAF mutation is associated with early stage disease and improved outcome in patients with low-grade serous ovarian cancer
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.
Copyright © 2012 American Cancer Society.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3961140/bin/nihms-436872-f0001.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3961140/bin/nihms-436872-f0002.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3961140/bin/nihms-436872-f0003.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3961140/bin/nihms-436872-f0003.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3961140/bin/nihms-436872-f0005.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3961140/bin/nihms-436872-f0005.gif)
Similar articles
-
Clinicopathologic and Molecular Features of Paired Cases of Metachronous Ovarian Serous Borderline Tumor and Subsequent Serous Carcinoma.Am J Surg Pathol. 2019 Nov;43(11):1462-1472. doi: 10.1097/PAS.0000000000001325. Am J Surg Pathol. 2019. PMID: 31343420 Free PMC article.
-
Molecular diagnosis in type I epithelial ovarian cancer.Ginekol Pol. 2017;88(12):692-697. doi: 10.5603/GP.a2017.0123. Ginekol Pol. 2017. PMID: 29303228 Review.
-
Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation status in codon 600 in borderline and low-grade ovarian cancers.Tumour Biol. 2017 May;39(5):1010428317706230. doi: 10.1177/1010428317706230. Tumour Biol. 2017. PMID: 28488545
-
Low Grade Serous Ovarian Carcinoma: from the molecular characterization to the best therapeutic strategy.Cancer Treat Rev. 2015 Feb;41(2):136-43. doi: 10.1016/j.ctrv.2014.12.003. Epub 2014 Dec 23. Cancer Treat Rev. 2015. PMID: 25573350 Review.
-
KRAS (but not BRAF) mutations in ovarian serous borderline tumour are associated with recurrent low-grade serous carcinoma.J Pathol. 2013 Dec;231(4):449-56. doi: 10.1002/path.4252. J Pathol. 2013. PMID: 24549645 Free PMC article.
Cited by
-
Advances in precision therapy of low-grade serous ovarian cancer: A review.Medicine (Baltimore). 2024 Apr 26;103(17):e34306. doi: 10.1097/MD.0000000000034306. Medicine (Baltimore). 2024. PMID: 38669365 Free PMC article. Review.
-
In Silico Approach to Molecular Profiling of the Transition from Ovarian Epithelial Cells to Low-Grade Serous Ovarian Tumors for Targeted Therapeutic Insights.Curr Issues Mol Biol. 2024 Feb 26;46(3):1777-1798. doi: 10.3390/cimb46030117. Curr Issues Mol Biol. 2024. PMID: 38534733 Free PMC article.
-
Complexity of the Genetic Background of Oncogenesis in Ovarian Cancer-Genetic Instability and Clinical Implications.Cells. 2024 Feb 15;13(4):345. doi: 10.3390/cells13040345. Cells. 2024. PMID: 38391958 Free PMC article. Review.
-
Mesonephric and mesonephric-like adenocarcinomas of gynecologic origin: A single-center experience with molecular characterization, treatment, and oncologic outcomes.Gynecol Oncol. 2024 Mar;182:32-38. doi: 10.1016/j.ygyno.2024.01.015. Epub 2024 Jan 20. Gynecol Oncol. 2024. PMID: 38246044
-
Molecular Status of BRAF Mutation in Epithelial Ovarian Cancer: An Analysis of 57 Cases in the Northeast of Iran.Iran J Pathol. 2023 Spring;18(2):134-139. doi: 10.30699/IJP.2023.554750.2907. Epub 2023 Jun 20. Iran J Pathol. 2023. PMID: 37600581 Free PMC article.
References
-
- Ho CL, et al. Mutations of BRAF and KRAS precede the development of ovarian serous borderline tumors. Cancer Res. 2004;64(19):6915–8. - PubMed
-
- Mayr D, et al. KRAS and BRAF mutations in ovarian tumors: a comprehensive study of invasive carcinomas, borderline tumors and extraovarian implants. Gynecol Oncol. 2006;103(3):883–7. - PubMed
-
- Sieben NL, et al. In ovarian neoplasms, BRAF, but not KRAS, mutations are restricted to low-grade serous tumours. J Pathol. 2004;202(3):336–40. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials
Miscellaneous