Objective: To investigate the role of DNA methyltransferases (DNMT) in carcinogenesis and development of salivary adenoid cystic carcinoma (ACC) by detection the expression of DNMT in ACC and to assess its correlation to methylation of tumor suppressor genes and biological behavior of ACC.
Methods: The protein expression of DNMT1 and DNMT3b were examined by immunohistochemistry in paraffin-embedded tissues of ACC from 60 patients. The association between the positive staining of DNMT1 and DNMT3b microscopically and the CpG islands methylation status of some tumor suppressor genes, tumor grade and stage was analysed by Fisher exact test.
Results: The number of DNMT1 positive cells was much more than that of DNMT3b (P < 0.01). The positive expression of DNMT1 was increased concomitantly to the amounts of methylation of tumor suppressor genes occurred in ACC and was significantly correlated to the methylation status of RASSF1A (P < 0.01). A difference was found between the more and less methylation of tumor suppressor genes group (P < 0.05) The increased positive expression of DNMT1 correlated to the tumor grade (P < 0.05) and stage (P < 0.01). It was much more expressed in the lower grade or more advanced stage cases. The correlation between the expression of DNMT3b and the methylation of tumor suppressor genes, tumor grade and stage was not found.
Conclusions: DNMT1 may play an important role in the maintenance of methylation of tumor suppressor genes in ACC and was related correlated to the methylation of RASSF1A, tumor grade and stage, which implied that DNMT1 may contribute to the carcinogenesis and development of ACC and was likely to be a molecular marker for evaluating the prognosis of patients with ACC.