The promoter methylation of tissue inhibitor of metalloproteinase 3 in cardia carcinoma and its clinical significance / 肿瘤研究与临床

ABSTRACT

Objective To explore the relations among the promoter methylation of tissue inhibitor of metalloproteinase-3 (TIMP-3) gene and its protein expression, and the clinicopathological features in the gastric cardia carcinoma. Methods The tumor tissues and the adjacent normal mucosal tissues were collected from 65 patients with cardia carcinoma. The promoter methylation levels and the protein expression of TIMP-3 gene were detected by methylation-specific PCR (MSP) and immunohistochemistry respectively. Results The TIMP-3 methylation rates was 78.5 % (51/65) in the tumor tissues and 13.8 % (9/65) in the incisal edge of normal tissues, the methylation rates of TIMP-3 had positive correlation with the size of tumor, invasion depth, lymphatic metastasis and the stage of tumor. The protein expression of TIMP-3 was 26.2 %(17/65) in the tumor tissues and 95.4 % (62/65) in the incisal edge of normal tissues (P = 0.016), the protein expression of TIMP-3 was negatively correlated with the size of tumor, invasion depth, lymphatic metastasis and the stage of tumor. Conclusion The methylation of promoter region in CpG islands is a main mechanism of reduced and loss expression of TIMP-3 gene, which may play an important role in the invasion and metastasis of cardia carcinoma.