Clinical significance of the expression of DNA methyltransferase proteins in gastric cancer.

DNA methyltransferase (DNMT) 1, DNMT3A and DNMT3B, which affect promoter CpG methylation status, play a significant role in cancer development. Little is known regarding the clinical significance of DNMT expression in gastric cancers. Expression of DNMT1, DNMT3A and DNMT3B in paraffin sections from 54 gastric cancer patients were examined using immunohistochemistry, and their associations with the corresponding clinicopathological parameters were analyzed using the Chi-square test. Overexpression of DNMT1, DNMT3A and DNMT3B in gastric cancer tissues was observed in 35 (64.8%), 38 (70.4%) and 28 (51.9%) of 54 cases, respectively. DNMT1 was localized in the cytoplasm and nuclei of the cancer cells, whereas DNMT3A and DNMT3B were detected only in the cytoplasm. DNMT1 expression was more frequently found in tumors localizing at the cardia or body of the stomach (P=0.048). DNMT3A was associated with TNM stage (P=0.001) and lymph node metastasis (P=0.002). No significant correlation was found between DNMT3B expression and clinicopathological data (P>0.05). The co-expression of DNMT1 and DNMT3A, and of DNMT3A and DNMT3B was more frequently found in tumors localizing at the cardia or body of the stomach (P=0.005 and P=0.009 respectively). Moreover, co-expression of DNMT1 and DNMT3A was significantly associated with lymph node metastasis (P=0.035). DNMTs are overexpressed in gastric cancer, and may play a significant role in the development of aberrant promoter methylation during tumorigenesis.