BRAF V600E Expression by Immunohistochemistry in Colon Cancer and Clinico-pathologic Features Associated with BRAF-Mutated Colonic Cancers in Mexican Patients

  • Karla J. González-Colunga
  • Leonardo S. Lino-SilvaEmail author
  • Rosa A. Salcedo-Hernández
  • Erika B. Ruiz-García
  • César Zepeda-Najar
Original Research



BRAF evaluation is currently limited to molecular techniques, which are expensive and not widely available to practicing pathologists. Our objective was to determine the diagnostic performance of immunohistochemistry (IHC) against BRAF V600E for BRAF mutation and the secondary objective was determining histopathological characteristics of colon carcinomas with BRAF mutated.


Cases of adenocarcinoma of the colon with a known BRAF mutation status were identified from the pathological files of our institution.


We analyzed 135 cases, 13 cases had the BRAF mutation (9.6%) and 122 were non-mutated. The mutated cases expressed intense and diffusely the anti-antibody against BRAF V600E, and 119 (97.5%) of the 122 cases without mutation were negative and the remaining 3 were focal and weakly positive. The IHC demonstrated a sensitivity of 100%, specificity of 97.5%, positive predictive value of 81.3% (95% CI = 56.9 to 93.4%), negative predictive value of 100% (95% CI = 89 to 100%), and an overall accuracy of 97.8%. The only significant clinicopathological differences between cancers with BRAF mutated compared with BRAF non-mutated were that mutated had less lymph node metastases (23% vs. 68.1%) and the tumor size was greater (median 90 mm vs. 60 mm). The survival between groups was not statistically significant.


IHC against BRAF V600E showed an excellent performance, making it feasible as an alternative for molecular examination. Tumors with BRAF mutated did not show distinctive clinico-pathological characteristics, except for a larger tumor size.


BRAF Molecular pathology Colon cancer Immunohistochemistry Diagnostic test 


Compliance with Ethical Standards

This study was carried out following the guidelines from Helsinski declaration and was approved for the Etics in Investigation Review Board of our Institution. Due to the retrospective nature of the study informed consent was not required.

Conflict Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Wish TA, Hyde AJ, Parfrey PS, Green JS, Younghusband HB, Simms MI, et al. Increased cancer predisposition in family members of colorectal cancer patients harboring the p.V600E BRAF mutation: a population based study. Cancer Epidemiol Biomark Prev. 2010;19:1831–9.CrossRefGoogle Scholar
  2. 2.
    Zlobec I, Bihl MP, Schwarb H, Terracciano L, Lugli A. Clinicopathological and protein characterization of BRAF- and K-RAS-mutated colorectal cancer and implications for prognosis. Int J Cancer. 2010;127(2):367–80.Google Scholar
  3. 3.
    De Roock W, Claes B, Bernasconi D. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010;11:753–62.CrossRefGoogle Scholar
  4. 4.
    Lochhead P, Kuchiba A, Imamura Y, Liao X, Yamauchi M, Nishihara R, et al. Microsatellite instability and BRAF mutation testing in colorectal cancer prognostication. J Natl Cancer Inst. 2013;105:1151–6.CrossRefGoogle Scholar
  5. 5.
    Capper D, Voigt A, Bozukova G, Ahadova A, Kickingereder P, von Deimling A, et al. BRAF V600E-specific immunohistochemistry for the exclusion of Lynch syndrome in MSI-H colorectal cancer. Int J Cancer. 2013;133:1624–30.CrossRefGoogle Scholar
  6. 6.
    Capper D, Berghoff AS, Magerle M, Ilhan A, Wöhrer A, Hackl M, et al. Immunohistochemical testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases. Acta Neuropathol. 2012;123:223–33.CrossRefGoogle Scholar
  7. 7.
    Chen D, Huang J-F, Liu K, Zhang L-Q, Yang Z, Chuai ZR, et al. BRAFV600E mutation and its association with clinicopathological features of colorectal cancer: a systematic review and meta-analysis. PLoS One. 2014;9(3):e90607.CrossRefGoogle Scholar
  8. 8.
    Clancy C, Burke JP, Kalady MF, Coffey JC. BRAF mutation is associated with distinct clinicopathological characteristics in colorectal cancer: a systematic review and meta-analysis. Color Dis. 2013;15(12):e711–8.CrossRefGoogle Scholar
  9. 9.
    Li WQ, Kawakami K, Ruszkiewicz A, Bennett G, Moore J. Iacopetta B. BRAF mutations are associated with distinctive clinical, pathological and molecular features of colorectal cancer independently of microsatellite instability status. Mol Cancer. 2006;5:2.CrossRefGoogle Scholar
  10. 10.
    Dvorak K, Higgins A, Palting J, Cohen M, Brunhoeber P. Immunohistochemistry with anti-BRAF V600E (VE1) mouse monoclonal antibody is a sensitive method for detection of the BRAF V600E mutation in colon cancer: evaluation of 120 cases with and without KRAS mutation and literature review. Pathol Oncol Res. 2017 (early online publication).
  11. 11.
    Affolter K, Samowitz W, Tripp S, Bronner MP. BRAF V600E mutation detection by immunohistochemistry in colorectal carcinoma. Genes Chromosom Cancer. 2013;52:748–52.CrossRefGoogle Scholar
  12. 12.
    Bledsoe JR, Kamionek M, Mino-Kenudson M. BRAF V600E immunohistochemistry is reliable in primary and metastatic colorectal carcinoma regardless of treatment status and shows high intratumoral homogeneity. Am J Surg Pathol. 2014;38(10):1418–28.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Surgical PathologyInstituto Nacional de CancerologíaMexico CityMexico
  2. 2.Gastrointestinal Pathology DivisionInstituto Nacional de Cancerología de México (Mexico’s National Cancer Institute)Mexico CityMexico
  3. 3.Surgical OncologyInstituto Nacional de CancerologíaMexico CityMexico
  4. 4.Medical OncologyInstituto Nacional de CancerologíaMexico CityMexico
  5. 5.Surgical OncologyHospital Ángeles TijuanaTijuanaMexico

Personalised recommendations