Utility of BRAF V600E mutation-specific immunohistochemistry in detecting BRAF V600E-mutated gastrointestinal stromal tumors.
OBJECTIVE
As patients with BRAF V600E mutation respond to BRAF inhibitors, it is important to identify these mutations to stratify patients for the appropriate therapy. In this study, we evaluated the utility of a BRAF V600E allele-specific antibody in gastrointestinal stromal tumors (GISTs).


METHODS
BRAF V600E mutation-specific immunohistochemistry (negative, weak, or moderate/strong expression) and BRAF sequencing were performed on 38 consecutive GISTs diagnosed between January 2013 and April 2014.


RESULTS
GISTs from a cohort of 25 men and 13 women (mean age, 61 years; range, 39-88 years) were localized to the stomach (18), small bowel (10), colon (three), rectum (two), and pelvis/omentum (five). Strong and diffuse cytoplasmic BRAF expression was noted in two (5%) of 38 cases, while eight (21%) of 38 cases showed weak staining, and 28 (74%) of 38 cases were negative. Both of the strongly positive cases arose in the stomach, occurring in a 42-year-old and a 47-year-old woman, respectively. The lesions measured 0.8 and 1 cm, showed spindle cell morphology, and had no risk of progressive disease by Miettinen criteria. Both cases showed heterozygous BRAF V600E, while no BRAF mutations were detected in cases with weak or negative BRAF expression.


CONCLUSIONS
BRAF V600E mutation-specific immunohistochemistry is a highly sensitive and specific method for detecting BRAF-mutated GISTs.
From the Robert J. Tomsich Pathology and Laboratory Medicine Institute, Department of Pathology, Cleveland Clinic, Cleveland, OH; patild@ccf.org rubinb2@ccf.org.
Deepa T
DT
Patil
From the Robert J. Tomsich Pathology and Laboratory Medicine Institute, Department of Pathology, Cleveland Clinic, Cleveland, OH;
Shuang
S
Ma
Department of Pathology, Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science, Shiga, Japan and.
Mai
M
Konishi
From the Robert J. Tomsich Pathology and Laboratory Medicine Institute, Department of Pathology, Cleveland Clinic, Cleveland, OH;
Paula D
PD
Carver
Knight Diagnostic Laboratories, Oregon Health and Science University, Portland.
Marina
M
Pukay
Knight Diagnostic Laboratories, Oregon Health and Science University, Portland.
Carol
C
Beadling
Knight Diagnostic Laboratories, Oregon Health and Science University, Portland.
Christopher L
CL
Corless
From the Robert J. Tomsich Pathology and Laboratory Medicine Institute, Department of Pathology, Cleveland Clinic, Cleveland, OH;
Brian P
BP
Rubin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
BRAF V600E; Gastrointestinal stromal tumor; Immunohistochemistry