Immunohistochemical study of BRAF V600E mutant protein expression in high-grade sarcomas

Alfredo L. Valente, Kerry Whiting, Jamie Tull, Charlene Maciak, Shengle Zhang


BRAF V600E is a mutation present in numerous neoplasms, including melanomas, thyroid, colorectal and ovarian carcinomas, gastrointestinal stromal tumors, and Langerhans’ cell histiocytosis. Vemurafenib, a BRAF V600E kinase inhibitor has been successfully used in the treatment of melanoma. The role of this mutation in unclassified high-grade sarcomas, malignancies with very limited treatment options, has not been widely studied.  Because of the availability of a highly sensitive and specific antibody (VE1) against the BRAF V600E mutant protein, we tested 48 cases of unclassified high-grade sarcomas. Cytoplasmic expression intensity was graded as negative (0), or positive (2+ or 3+) by two pathologists and a pathology resident.  Forty one out of 48 specimens remained intact in the cores after immunohistochemistry (IHC) processing.  Six of the 41 cases (15%) were scored as positive. In addition, non-specific nuclear staining was detected in 12/88 cores (14%). The 6 positive cases were tested for the BRAF V600E mutation by RT-PCR, and all were negative. Based on these results, we concluded that BRAF V600E mutation is rare in unclassified high-grade sarcomas, and because of the non-specific staining, results should be interpreted with caution.

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Journal of Solid Tumors

ISSN 1925-4067(Print)   ISSN 1925-4075(Online)

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