p16INK4a hypermethylation and p53, p16 and MDM2 protein expression in Esophageal Squamous Cell Carcinoma

<p>Abstract</p> <p>Background</p> <p>Tumor suppressor genes <it>p53 </it>and <it>p16</it>^INK4aand the proto-oncogene <it>MDM2 </it>are considered to be essential G1 cell cycle regulatory genes whose loss of function is associated with ESCC carcinogenesis. We assessed the aberrant methylation of the <it>p16 </it>gene and its impact on <it>p16</it>^{<it>INK4a </it>}protein expression and correlations with <it>p53 </it>and <it>MDM2 </it>protein expressions in patients with ESCC in the Golestan province of northeastern Iran in which ESCC has the highest incidence of cancer, well above the world average.</p> <p>Methods</p> <p>Cancerous tissues and the adjacent normal tissue obtained from 50 ESCC patients were assessed with Methylation-Specific-PCR to examine the methylation status of <it>p16</it>. The expression of <it>p16</it>, <it>p53 </it>and <it>MDM2 </it>proteins was detected by immunohistochemical staining.</p> <p>Results</p> <p>Abnormal expression of <it>p16 </it>and <it>p53</it>, but not <it>MDM2</it>, was significantly higher in the tumoral tissue. <it>p53 </it>was concomitantly accumulated in ESCC tumor along with <it>MDM2 </it>overexpression and <it>p16 </it>negative expression. Aberrant methylation of the <it>p16</it>^{<it>INK4a </it>}gene was detected in 31/50 (62%) of esophageal tumor samples, while two of the adjacent normal mucosa were methylated (P < 0.001). <it>p16</it>^{<it>INK4a </it>}aberrant methylation was significantly associated with decreased <it>p16 </it>protein expression (P = 0.033), as well as the overexpression of <it>p53 </it>(P = 0.020).</p> <p>Conclusions</p> <p><it>p16 </it>hypermethylation is the principal mechanism of <it>p16 </it>protein underexpression and plays an important role in ESCC development. It is associated with p53 protein overexpression and may influence the accumulation of abnormally expressed proteins in <it>p53-MDM2 </it>and <it>p16-Rb </it>pathways, suggesting a possible cross-talk of the involved pathways in ESCC development.</p

Primary Angle Closure Glaucoma-associated Genetic Polymorphisms in Northeast Iran

Purpose: To evaluate the association of five different polymorphisms from a genomewide- associated study with susceptibility to glaucoma in the northeast Iranian population. Methods: Hundred and thirty patients with primary angle closure glaucoma (PACG) and 130 healthy controls were genotyped for the polymorphic regions with the aid of tetraamplification refractory mutation system-polymerase chain reaction. The association of these variants with the disease susceptibility was measured statistically with the logistic regression method. Results: Hundred and thirty patients with PACG (53 males, 77 females) with a mean age of 64.5 ± 6.2 years and 130 healthy control subjects (51 males, 79 females) with a mean age of 64.0 ± 5.7 years were selected for evaluation. There was a significant association between rs3816415 (P = 0.005), rs736893 (P &lt; 0.001), rs7494379 (P &lt; 0.001), and rs1258267 (P = 0.02) with PACG susceptibility. This association could not be shown for rs3739821. Conclusion: It was revealed that studied variants in GLIS3, EPDR1, FERMT2, and CHAT genes can contribute to the incidence of PACG. Additional studies in other populations are needed to evaluate DPM2-FAM102A