Search

Aims Adenoid cystic carcinoma (Ad CC) is one of the most common salivary gland malignancies and the long-term prognosis is poor. In this study, we examined alterations of Ad CC-associated genes, MYB, MYBL1, MYBL2 and NFIB, and their target molecules, including MYC. The results were correlated to clinicopathological profile of the patients. Methods and results Using paraffin tumour sections from 33 cases of salivary gland Ad CC, we performed a detailed fluorescence in-situ hybridization ( FISH) analysis for gene splits and fusions of MYB, MYBL1, MYBL2 and NFIB. We found that 29 of 33 (88%) Ad CC cases showed gene splits in either MYB, MYBL1 or NFIB. None of the cases showed an MYBL2 gene alteration. Ad CCs were divided genetically into six gene groups, MYB- NFIB ( n = 16), MYB-X ( n = 4), MYBL1- NFIB ( n = 2), MYBL1-X ( n = 1), NFIB-X ( n = 6) and gene-split-negative ( n = 4). Ad CC patients showing the MYB or MYBL1 gene splits were associated with microscopically positive surgical margins ( P = 0.0148) and overexpression of MYC ( P = 0.0164). MYC expression was detected in both ductal and myoepithelial tumour cells, and MYC overexpression was associated with shorter disease-free survival of the patients ( P = 0.0268). Conclusions The present study suggests that (1) nearly 90% of Ad CCs may have gene alterations of either MYB, MYBL1 or NFIB, suggesting the diagnostic utility of the FISH assay, (2) MYB or MYBL1 gene splits may be associated with local aggressiveness of the tumours and overexpression of MYC, which is one of the oncogenic MYB/ MYBL1 targets and (3) MYC overexpression may be a risk factor for disease-free survival in Ad CC. [ABSTRACT FROM AUTHOR]

Aims Cancer/testis antigens ( CTAs) are detected in cancer cells but not in healthy normal tissues, with the exception of gametogenic tissues. CTAs are highly immunogenic proteins, and thus represent ideal targets for cytotoxic T-lymphocyte-mediated specific immune therapy. The aim of this study was to screen CTA expression in various types of salivary gland carcinoma and to clarify clinicopathological significance of MAGE-A and NY- ESO-1 expression in adenoid cystic carcinomas (AdCCs) of the salivary gland, which is one of the most common salivary gland carcinomas, and usually has a fatal outcome. Methods and results We used immunohistochemistry to examine the expression of four CTAs ( MAGE-A, NY- ESO-1, CT7, and GAGE7) in various types of salivary gland carcinoma ( n = 95). When carcinoma cases were divided into low-grade and intermediate/high-grade types, NY- ESO-1 and CT7 were expressed more frequently in intermediate/high-grade carcinomas. We then focused on MAGE-A and NY- ESO-1 expression in a large cohort of adenoid cystic carcinomas (Ad CCs) ( n = 46). MAGE-A and NY- ESO-1 were frequently expressed in Ad CC; specifically, MAGE-A was expressed in >60% of the Ad CC cases. MAGE-A expression and tumour site (minor salivary gland) were identified as independent risk factors for locoregional tumour recurrence. Conclusions These findings suggest that CTAs may be expressed in a variety of salivary gland carcinomas, especially in those with higher histological grades. In addition, MAGE-A, which is frequently expressed in Ad CC cases, may be a useful prognostic factor for poorer locoregional recurrence-free survival. [ABSTRACT FROM AUTHOR]