Examination of MYB in Adenoid Cystic Carcinoma and Other Neoplasms of the Head & Neck.
Louis B Brill, William A Kanner, Christopher A Moskaluk, Ywonne Andren, Andre Fehr, Goran Stenman, Henry F Frierson. University of Virginia, Charlottesville; University of Gothenburg, Sweden
Background: Adenoid cystic carcinomas (ACC) are characterized by a recurrent and tumor type-specific t(6;9)(q22-23;p23-24) chromosomal translocation. Recent studies have shown that this translocation results in a novel fusion of the MYB oncogene with the transcription factor gene NFIB in ACC arising in several anatomic sites including the salivary glands. In this study of ACC and other neoplasms of the head & neck, we explored the diagnostic utility of an antibody that recognizes residues near the N-terminus of MYB and compared the results with the expression of MYB-NFIB fusion transcripts.
Design: We immunostained 68 cases of ACC of various anatomic sites and 113 non-ACC tumors of the head and neck. An anti-MYB rabbit monoclonal antibody (clone EP769Y,1:200 dilution, Epitomics, Inc.) was used after pressure cooker antigen retrieval. MYB immunostaining was considered positive if greater than 5% of tumor cells displayed strong nuclear staining. RT-PCR and nucleotide sequence analysis were used to determine the MYB-NFIB gene fusion status, while quantitative real-time PCR was employed to examine MYB expression levels.
Results: 53 ACC arose in the aerodigestive tract, while 15 were from other sites. 82% of ACC were positive for MYB compared with 14% of non-ACC neoplasms. The sensitivity and specificity of MYB immunostaining for ACC was 82% and 86%, respectively. There was no difference in staining according to the grade of ACC, but a peculiar zonal pattern of staining was observed in various cases. Approximately 70% of a subset of ACCs (n=30) were fusion-positive and these also were consistently positive by IHC. Non-ACC tumors that stained positive for MYB were typically fusion-negative. Analysis of the expression levels of MYB by quantitative real-time PCR showed that 90% of the fusion-positive cases also expressed high levels of MYB transcripts.
Conclusions: Fusion-positive ACC typically express high levels of MYB transcripts and are positive for MYB with IHC. MYB immunostaining is sensitive and specific for the diagnosis of ACC, but some non-ACC neoplasms in the differential diagnosis are also labeled. The zonal pattern of positive and negative staining observed in some cases may relate to issues of formalin fixation and relatively brief half-life of the protein.
Category: Head & Neck
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 148, Wednesday Morning