Karla J González-Colunga1, Leonardo S Lino-Silva2,3, Rosa A Salcedo-Hernández4, Erika B Ruiz-García5, César Zepeda-Najar6. 1. Surgical Pathology, Instituto Nacional de Cancerología, Mexico City, Mexico. 2. Surgical Pathology, Instituto Nacional de Cancerología, Mexico City, Mexico. saul.lino.sil@gmail.com. 3. Gastrointestinal Pathology Division, Instituto Nacional de Cancerología de México (Mexico's National Cancer Institute), Av. San Fernando # 22, Sección XVI, Tlalpan, 14080, Mexico City, Mexico. saul.lino.sil@gmail.com. 4. Surgical Oncology, Instituto Nacional de Cancerología, Mexico City, Mexico. 5. Medical Oncology, Instituto Nacional de Cancerología, Mexico City, Mexico. 6. Surgical Oncology, Hospital Ángeles Tijuana, Tijuana, Baja California Norte, Mexico.
Abstract
BACKGROUND: 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. METHODS: Cases of adenocarcinoma of the colon with a known BRAF mutation status were identified from the pathological files of our institution. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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 BRAFV600E for BRAF mutation and the secondary objective was determining histopathological characteristics of colon carcinomas with BRAF mutated. METHODS: Cases of adenocarcinoma of the colon with a known BRAF mutation status were identified from the pathological files of our institution. RESULTS: 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 BRAFV600E, 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. CONCLUSION: IHC against BRAFV600E 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.
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