BRAF Mutation is associated with early stage disease and improved outcome in patients with low-grade serous ovarian cancer Journal Article


Authors: Grisham, R. N.; Iyer, G.; Garg, K.; DeLair, D.; Hyman, D. M.; Zhou, Q.; Iasonos, A.; Berger, M. F.; Dao, F.; Spriggs, D. R.; Levine, D. A.; Aghajanian, C.; Solit, D. B.
Article Title: 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. Cancer 2013. © 2012 American Cancer Society.
Keywords: adult; cancer survival; controlled study; human tissue; treatment response; aged; gene mutation; major clinical study; overall survival; histopathology; cancer adjuvant therapy; cancer staging; outcome assessment; follow up; ovarian cancer; gene; ovary cancer; amino acid substitution; genetic association; mutational analysis; survival time; early cancer; gene identification; oncogene k ras; k ras protein; outcomes; b raf kinase; braf; cancer morphology; braf gene; cancer prognosis; early stage disease; low-grade serous ovarian cancer; low grade serous ovary cancer
Journal Title: Cancer
Volume: 119
Issue: 3
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2013-02-01
Start Page: 548
End Page: 554
Language: English
DOI: 10.1002/cncr.27782
PROVIDER: scopus
PUBMED: 22930283
PMCID: PMC3961140
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 1 March 2013" - "CODEN: CANCA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. David Solit
    431 Solit
  2. Douglas A Levine
    356 Levine
  3. Qin Zhou
    120 Zhou
  4. Alexia Elia Iasonos
    179 Iasonos
  5. Gopakumar Vasudeva Iyer
    125 Iyer
  6. Rachel Nicole Grisham
    35 Grisham
  7. David Hyman
    181 Hyman
  8. David R Spriggs
    309 Spriggs
  9. Michael Forman Berger
    380 Berger
  10. Karuna Garg
    74 Garg
  11. Deborah F DeLair
    86 DeLair
  12. Fanny Dao
    56 Dao