No evidence for BRAF-V600E mutations in gastroeosophageal tumors: results from a high-throughput analysis of 534 cases using a mutation-specific antibody.
BACKGROUND
BRAF-V600E mutations are found in a broad spectrum of cancer types and can be successfully targeted by specific therapeutic compounds. Little data on the prevalence of BRAF-V600E mutations in tumors of the upper gastrointestinal tract are available.


METHODS
We constructed tissue microarrays of formalin-fixed and paraffin-embedded specimens of 534 gastroesophageal tumors (119 squamous cell cancers and 72 adenocarcinomas of the esophagus, 63 cancers of the gastroesophageal junction/cardia, 199 gastric cancers of the corpus or antrum, 81 gastric gastrointestinal stromal tumors) and performed anti-BRAF-V600E immunostaining using the mutation-specific antibody VE1. As control tissue we used 3 melanoma cases with confirmed BRAF-V600E mutation and distinct VE1 immunostaining.


RESULTS
None of the gastroesophageal tumor cases showed a positive immunostaining signal.


CONCLUSIONS
BRAF-V600E mutation is not a relevant oncogenic driver in gastroesophageal tumors. Immunohistochemical analysis using mutation-specific antibodies on tissue microarrays is a feasible, time-efficient and cost-efficient approach to high-throughput screening for specific mutations in large tumor series.
Departments of *Medicine I ¶Surgery ‡Institute of Neurology #Clinical Institute of Pathology †Comprehensive Cancer Center-Gastro-Esophageal Cancers Unit (CCC-GET), Medical University of Vienna §Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University ∥Clinical Cooperation Unit Neuropathology, DKFZ, Heidelberg, Germany.
Matthias
M
Preusser
Anna S
AS
Berghoff
David
D
Capper
Andreas
A
von Deimling
Florian
F
Maroske
Thomas
T
Brodowicz
Michael
M
Hejna
Peter
P
Birner
Sebastian F
SF
Schoppmann
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000368:Aged; D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D057166:High-Throughput Screening Assays; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016612:Paraffin Embedding; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D046888:Tissue Array Analysis
D000911:Antibodies, Monoclonal; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf