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Mod Pathol. 2015 Apr;28(4):596-606. doi: 10.1038/modpathol.2014.150. Epub 2014 Nov 21.

Cross-reactivity of the BRAF VE1 antibody with epitopes in axonemal dyneins leads to staining of cilia.

Author information

1
Division of Neuropathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2
Monoclonal Antibody Core, Dana-Farber Cancer Institute and Dana-Farber/Harvard Cancer Center, Harvard Medical School, Boston, MA, USA.
3
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
4
1] Division of Neuropathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Abstract

Antibodies that recognize neo-epitopes in tumor cells are valuable tools in the evaluation of tissue biopsy or resection specimens. The VE1 antibody that recognizes the V600E-mutant BRAF protein is one such example. We have recently shown that the vast majority of papillary craniopharyngiomas-tumors that arise in the sellar or suprasellar regions of the brain-harbor BRAF V600E mutations. The VE1 antibody can be effective in discriminating papillary craniopharyngioma from adamantinomatous craniopharyngioma, which harbors mutations in CTNNB1 and not BRAF. While further characterizing the use of the VE1 antibody in the differential diagnosis of suprasellar lesions, we found that the VE1 antibody stains the epithelial cells lining Rathke's cleft cysts with very strong staining of the cilia of these cells. We used targeted sequencing to show that Rathke's cleft cysts do not harbor the BRAF V600E mutation. Moreover, we found that the VE1 antibody reacts strongly with cilia in various structures-the bronchial airways, the fallopian tubes, the nasopharynx, and the epididymis-as well as with the flagella of sperm. In addition, VE1 reacts strongly with the cilia of the ependymal lining of the brain and with the cilia-containing microlumens of ependymoma tumors. There is significant sequence homology between the synthetic peptide (amino acid 596-606 of BRAF V600E: GLATEKSRWSG) that was used to generate the VE1 antibody and regions of multiple axonemal dynein heavy chain proteins (eg, DNAH2, DNAH7, and DNAH12). These proteins are major components of the axonemes of cilia and flagella where they drive the sliding of microtubules. In ELISA assays, we show that the VE1 antibody recognizes epitopes from these proteins. A familiarity with the cross-reactivity of the VE1 antibody with epitopes of proteins in cilia is of value when evaluating tissues stained with this important clinical antibody.

PMID:
25412847
DOI:
10.1038/modpathol.2014.150
[Indexed for MEDLINE]
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