RESUMO
OBJECTIVE: The progression of pleomorphic adenoma (PA) to carcinoma ex-pleomorphic adenoma (CXPA) encompasses several genomic alterations involving complex pathways. Tumor suppressor genes seem to play important roles in the tumorigenesis of both tumors. The aim of this study was to evaluate copy number and methylation of tumor suppressor genes' status in PA and CXPA samples. STUDY DESIGN: Eight cases of PA, 2 cases of residual PA in CXPA, and 5 cases of CXPA were studied; the latter were classified according to invasiveness and histopathological subtype. Changes in 41 tumor suppressor genes were evaluated by multiplex ligation-probe dependent amplification analysis. RESULTS: Copy number losses of CASP8, MLH1, and RARB genes were associated with PA and CXPA, while KLK3 and AI69125 copy number losses were exclusive to CXPA. The sarcomatoid carcinoma showed more copy number alterations compared with other subtypes. Hypermethylation of RASSF1 was found mainly in PA and less frequently in malignant tumors. CONCLUSIONS: CASP8, MLH1, and RARB tumor suppressor genes were altered by copy number losses during PA progression to CXPA. Lastly, RASSF1 inactivation by methylation was also detected in both tumors.
