P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population

Objective. To investigate the prevalence of p16(INK4) (a), p14(ARF), tumor protein p53 (TP53), and human telomerase reverse transcriptase (hTERT) promoter hypermethylation in mucoepidermoid carcinomas (MECs) and search for a possible association between methylation status and clinicopathological parameters. Study design. DNA extracted from 35 formalin-fixed and paraffin-embedded MEC samples and 10 normal salivary gland (NSG) tissue samples was analyzed for the presence of promoter hypermethylation using methylation-specific polymerase chain reaction testing. Results. The percentages of gene hypermethylation in MECs versus NSGs were the following: p14: 100% versus 20% (P LT .001); p16: 60% versus 20% (P = .035); hTERT: 54.3% versus 20% (P = .078); and TP53: 31.4% versus 30% (P = .981). Multiple sites were found to be methylated in 86% of MECs compared with 10% in NSGs (P LT .001). TP53 and hTERT were more often methylated in lower clinical stages (P = .033 and P = .005, respectively). Conclusions. Hypermethylation of p14 appears to be an important event in the development of mucoepidermoid carcinoma. High frequency of gene hypermethylation and high incidence of methylation at multiple sites point to the importance of epigenetic phenomena in the pathogenesis of MECs, although with modest impact on clinical parameters

Incidence and clinical relevance of T(11;19) translocation in salivary gland mucoepidermoid carcinoma

Mucoepidermoid carcinoma (MEC) harbors a recurring t(11;19) translocation with an associated novel fusion oncogene-MECT1-MAML2. The CRTC1-MAML2oncogene disrupts normal cell-cycle and differentiation, contributing to tumor development. The objectives of this study were to establish the incidence of CRTC1-MAML2 fusion in Serbian patients and estimate its relevance as a genetic marker of MEC behavior. In this retrospective study, 20 cases of MEC of salivary glands were tested for the presence of CRTC1-MAML2 fusion using reverse transcriptase-polymerase chain reaction. Clinicopathological parameters and survival data were examined in relation to fusion status. The CRTC1-MAML2 fusion was detected in 40% of MECs and its presence was associated exclusively with low-intermediate grade tumor histology (P = 0.02) and favorable clinical outcome, with 100 % overall survival rate (P=0.046). The study has shown that the presence of the CRTC1-MAML2 fusion can serve as an additional diagnostic and prognostic marker for mucoepidermoid carcinomas