title: BRAFV600E Gene Mutation in Colonic Adenocarcinomas. Immunohistochemical Detection Using Tissue Microarray and Clinicopathologic Characteristics: An 86 Case Series.
abstract: The detection of BRAF mutation in colorectal cancer has several clinical applications: enabling the discrimination between sporadic and Lynch syndrome-related colorectal carcinoma, and providing warning of a poorer prognosis. Few immunohistochemical studies using whole-tissue tumor section staining have recently been performed on colorectal cancer. The aim of this study was to evaluate the detection of BRAF mutation by immunohistochemistry (IHC) on tissue microarray (TMA). IHC was performed with the BRAF-specific antibody using TMA on a retrospective series of 86 colonic adenocarcinomas with known BRAF status. IHC using BRAF-specific antibody allowed to detect 20/21 BRAF mutated colonic adenocarcinomas and 60/65 BRAF wild-type cases. The staining was equivocal because of equivocal staining in 4 cases and heterogeneity in 3 cases. When compared with TaqMan real-time PCR, the sensitivity and specificity were 95.2% and 92.3%, respectively. Comparison with the whole section immunostaining improved sensitivity to 100% and specificity to 95.4%. Furthermore, in this study we found that BRAF mutated colonic adenocarcinoma were significantly more frequent in women, older patients, and right-sided. Moreover, morphologic features significantly associated with BRAF mutation were: serrated adenocarcinoma subtype, adenocarcinomas with a mucinous component, high histologic grade, pushing margins, stromal inflammation. BRAF-specific antibody can be used on TMA to screen BRAF-mutated colorectal carcinomas. Cases with equivocal or heterogenous staining must be compared with whole section staining. Moreover, BRAF mutated colonic carcinomas have distinct clinical and histopathologic features.
authors.affiliation: *Laboratoire d'Anatomie Pathologique, Centre Hospitalier Universitaire de Reims ∥Laboratoire Pol Bouin, Service de Biologie Moléculaire ¶Service de Chirurgie Digestive #Service d'Hépato-Gastro-Entérologie et Cancérologie Digestive, Centre Hospitalier Universitaire de Reims †UMR CNRS/URCA N°7369, Faculté de Médecine de Reims ‡Laboratoire de Biologie Oncologique, Institut Jean Godinot §Plateforme de Génétique Moléculaire des Cancers de Champagne Ardenne, Reims, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Boulagnon
authors.forename: Oriane
authors.initials: O
authors.lastname: Dudez
authors.forename: Olivia
authors.initials: O
authors.lastname: Beaudoux
authors.forename: Véronique
authors.initials: V
authors.lastname: Dalstein
authors.forename: Reza
authors.initials: R
authors.lastname: Kianmanesh
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.forename: Marie-Danièle
authors.initials: MD
authors.lastname: Diebold
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf