A cautionary note on the immunohistochemical detection of braf v600e mutations in serrated lesions of the colon

摘要

To the editor: We read with great interest therecently published article by Mesteri et al1regarding immunohistochemical detection of BRAFmutations in serrated colonic polyps. Some types ofserrated polyps, particularly sessile serrated polyps(sessile serrated adenomas), frequently harbor BRAFc.1799T4A (p.V600E) mutations and presumablyrepresent precursor lesions to sporadic coloniccarcinomas with a high degree of microsatelliteinstability (MSI-H). Detection of BRAF mutationshelps distinguish sporadic MSI-H tumors from thoseassociated with Lynch syndrome since Lynchrelated adenocarcinomas virtually never harborBRAF mutations. BRAF status combined withtesting for microsatellite instability also providesimportant prognostic information. Recent evidenceindicates that MSI-H tumors with wild-type BRAFhave a better prognosis than those associated withBRAF mutations. Patients with microsatellitestable (MSS) tumors and mutations in BRAF havelower 5-year survival than those with MSI-H tumorsand those with BRAF wild-type MSS tumors.2(For a complete discussion of the molecularcarcinogenesis in colorectal carcinoma, the readeris referred to a recent review by Colussi et al.3)Evaluation of BRAF is currently limited to moleculartechniques, such as PCR and sequencing assays,which often require specialized laboratories and arenot widely available to practicing pathologists.Thus, simple and inexpensive methods to evaluateBRAF mutational status are of substantial clinicalinterest. The potential clinical utility of detectingBRAF mutations in sessile serrated polyps is lessclear. Although up to 80% of sessile serrated polypsand microvesicular hyperplastic polyps containmutated BRAF, most of these do not progress toadenocarcinoma; thus, BRAF mutations are neitherdiagnostic of sessile serrated polyps, nor do theyreliably identify polyps that are at risk for malignantprogression.