Objective The aim of this study was to explore MMP-2 and TIMP-3 expression in the gastric cardia carcinoma and with the relationship between the pathological stages.Methods Gastric cardia carcinoma surgical resection speciments of 115 cases were for the trial group.paraneoplastic gastric noncancerous tissues of 40 cases (the distance to cancer border>5 cm) as normal controls.The expression of MMP-2 and TIMP-3 was detected by two-step immunohistochemical method.The relationship of MMP-2 and TIMP-3 between clinicopathological stages was analyze. Results MMP-2 in carcinoma of the gastric cardia and the paraneoplastic tissues of organizations positive expression rates were 57.4%(66/115) and 40.0%(16/40) (P<0.05).MMP-2 expression was positively correlated with tumor size,tumor invasion depth,lymphatic metastasis and stage of tumor, which was negatively correlated with the prognosis of gastric cardia carcinoma (P<0.05).TIMP-3 in carcinoma of the gastric cardia and the paraneoplastic tissues of organizations positive expression rates were 48.7%(56/115) and 95.0%(38/40) (P<0.05).TIMP-3 expression was negatively correlated with tumor size,tumor invasion depth,lymphatic metastasis and stage of tumor, which was positively correlated with the prognosis of gastric cardia carcinoma. Conclusion The over expression of MMP-2 and the lost of TIMP-3 may play an important role in the invasion and metastasis of gastric cardia carcinoma.Combined MMP-2 and TIMP-3 detection may help to judge gastric cardia carcinoma development and to assess the prognosis of patients.

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.

Objective To explore the relationship of the methylation levels of tissue inhibitor of metalloproteinases 3 (TIMP-3) gene promoter CpG islands with the invasiveness and prognosis in cardia carcinoma. Methods The tumors tissues were collected from 65 patients with cardia carcinoma. The methylation levels of the promoter of TIMP-3 gene were detected by methylation-specific PCR (MSP), the mRNA expression levels of TIMP-3 gene were detected by RT-PCR. The relationship of TIMP-3 gene ectopic methylation with invasiveness and prognosis of the cardia carcinoma patients was analyzed. Results The positive expression rates of TIMP-3 mRNA in gastric cancer and normal gastric tissues were 53.8 % (35/65) and 96.9 % (63/65), respectively. The difference was not statistically significant(Fisher exact test, P=0.912). The positive rate of TIMP-3 mRNA was negatively correlated with the depth of tumor invasion and lymph node metastasis [mucosa and muscular vs. serosa and mucosa outside of the serosa and muscula: 83.3 % (10/12) vs. 45.3 % (24/53); with lymph node metastasis vs. without lymph node metastasis: 73.9 % (17/23) vs. 40.5 %(17/42)] (both P<0.05). There was a negative correlation between TIMP-3 gene promoter methylation and TIMP-3 mRNA expression (r=-0.276, P=0.026). The size of tumor and TIMP-3 gene promoter methylation were both the independent influencial factors of prognosis in cardia carcinoma (both P<0.05). Conclusion The methylation of promoter region in CpG islands plays an important role in the invasion and metastasis of cardia carcinoma, and it can be used as an independent predictor of biological behavior and prognosis.