Progressive genetic alterations of adenoid cystic carcinoma with high-grade transformation

Abstract

Context.-Although genome-wide imbalances have been characterized in conventional adenoid cystic carcinoma, other than p53 mutational status, the molecular profile of adenoid cystic carcinoma with high-grade transformation has not been explored. Objective.-To evaluate progressive genetic alterations in adenoid cystic carcinoma with high-grade transformation using array comparative genomic hybridization. Design.-Five adenoid cystic carcinomas with highgrade transformation (4 primary tumors and 1 paired metastasis) were selected and characterized at the DNA level by array comparative genomic hybridization on formalin-fixed paraffin-embedded tissue. Select alterations were validated by fluorescence in situ hybridization. Results.-Chromosomal gains were mostly confined to the areas of high-grade transformation while losses were seen only in the conventional areas. Chromosomal regions with significant gains included 8q24, 17q11.2-q12, 17q23, and 15q11-13. Regions that showed the significant losses included 9q34, 4p16, 1p36.1, and 11q22. Fluorescence in situ hybridization analysis demonstrated increases in CA4VC (8q24.12-q24.13) and a low level increases in ERBB2 (formerly HER2/neu) (17q11.2-q12) in cases showing gains by array comparative genomic hybridization in these regions. However, no tumor showed HER2/neu immunopositivity. Conclusions.-High-grade transformation in adenoid cystic carcinoma is a complex process that is reflected by several chromosomal alterations. Our findings implicate CMYC amplification in this progression, although the role of HER2/neu is still unclear. Other candidate oncogenes, particularly on chromosome 17q23, warrant investigation in this rare tumor.