Increased DNA methyltransferase 1 protein expression correlates significantly with intestinal histological type and gender in gastric carcinomas.

Purpose: Promoter hypermethylation and reduced expression of many genes have been found in gastric cancer. DNA methyltransferases are enzymes potentially affecting promoter hypermethylation.

Material And Methods: We analyzed proteins expression of DNA methyltransferase 1 and 3b by immunohistochemistry in 47 surgically resected gastric cancer samples for which clinicopathological characteristics, patient's outcome and methylation status of 11 selected tumor-related genes have been determined. Promoter methylation status of genes was assessed by methylation specific PCR.

Results: We found that DNMT1 and 3b were up-regulated in gastric cancer and were detected in 51.1% and 57.4% of cases, respectively. Co-expression of DNMT1 and 3b was detected in 44.7%. Correlations analysis have showed that DNMT1 overexpression was significantly correlated with gastric cancer of intestinal histological type (P=0.01) and with gender of patient (P=0.01). However, there was no correlation between DNMT1 and DNMT3b overexpression in cancer and patients outcome. Moreover, there were no clear relations between the proteins expression of DNMT1 and 3b and DNA methylation status of genes. But co-expression of DNMT1 and DNMT3b was significantly associated with promoter hypermethylation of RAR-β2 (P=0.04).

Conclusions: Results from our study indicate that DNMT1 and 3b were overexpressed and could be involved in gastric tumorigenesis of intestinal histological type in the case of Tunisian patients.