Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands

Background: Genetic studies of salivary gland neoplasms were mainly focused on chromosomal changes, and some specific patterns of chromosome translocations have been described. However, molecular alterations, in particular the role of HER-2/H-ras/c-myc signalling cascade in pleomorphic adenoma pathogenesis (PA), are less well characterized. In addition, data on single nucleotide polymorphisms (SNPs) as potential susceptibility factors for PA development are also quite scarce. Methods: Mutational analyses were performed by means of real-time PCR (HER-2 and c-myc amplification analysis), PCR-SSCP and sequencing (H-ras point mutation detection). Polymorphisms analysis was performed by PCR-RFLP (survivin and MMP-9 genes). Results: Amplification of HER-2 and c-myc has been found in 13% and 9% of PA cases respectively. Point mutations in H-ras codons 12/13 have been detected in 17% of PAs. No correlation could be established between these alterations and clinical characteristics of PAs, whereas they might play a role in a subset of malignant salivary gland tumours. As for survivin -31 G/C polymorphism, C allele carriers had a 4-fold decrease of the risk of developing PA (p=0.05). Carriers of the variant allele T of the -1562C/T SNP in MMP-9 gene had a 4-fold increase of the risk of developing PA (p LT 0.001). Conclusions: A longer follow-up of PA patients harbouring mutations could uncover a prognostic role of HER-2 and c-myc amplification as predictors of adenoma transformation into carcinoma. Both survivin and MMP-9 promoter polymorphisms represent susceptibility factors for the development of PAs in the Serbian population

Lymph node distribution in the d3 area of the right mesocolon: implications for an anatomically correct cancer resection. A postmortem study

Data on lymph node distribution in the right colon D3 area are scarce, especially for nodes posterior to the superior mesenteric vessels

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

High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors

Objectives: to investigate p16(INK4a) and p14(ARF) tumor suppressor gene methylation status, determine telomere length and assess the importance of these epigenetic and genetic parameters in the development of pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid salivary glands. Materials and Methods: Genomic DNA from paraffin-embedded samples of 50 pleomorphic adenomas and 10 carcinomas ex pleomorphic adenoma was subjected to methylation specific polymerase chain reaction for hypermethylation analyses and real time polymerase chain reaction for the relative telomere length calculations. Results: Promoter hypermethylation of the two genes was a very frequent event in both neoplasms between 60% and 90% of samples were hypermethylated - but without significant difference between the groups. The mean relative telomere length in the pleomorphic adenoma group was significantly increased in comparison to the control group (P = 0.00), and significantly decreased in comparison to the carcinoma group (P = 0.05). Telomeres were also longer in myxoid and cellular histological subtypes of adenomas than in the classic type (P = 0.044 and P = 0.018, respectively). Longer telomeres were more frequent in tumors with hypermethylated p14(ARF) alleles (P = 0.013). Conclusion: Promoter hypermethylations seems to be an important mechanism of p16(INK4a) and Pl4(ARF) inactivation in parotid gland tumors. Telomeric lengthening appears to be involved in the pathogenesis of both benign and malignant tumors of the parotid glands. (C) 2015 Elsevier Ltd. All rights reserved