食管癌中MMP-9及其mRNA的表达与肿瘤抑制基因p53表达的关系

Expression of MMP-9 and MMP-9 mRNA in Esophageal Carcinoma Its Correlation with Antioncogene p53

目的:观察基质金属蛋白酶9(MMP9)与MMP-9mRNA在食管癌组织及细胞中的表达与作用特点及其与肿瘤浸润、转移及肿瘤抑制基因p53表达之间的关系。方法:采用免疫组织化学法、原位分子杂交和酶谱法(zymography)分别检测食管癌组织中MMP9、p53蛋白和MMP-9mRNA的分布及其活性,并结合临床病理参数进行综合分析。结果:75例食管癌组织中有62例MMP9表达阳性,阳性率为82.7%,75例食管癌组织中有54例MMP-9mRNA表达阳性,阳性率为72.0%,与对照组比较均有显著性差异(P<0.01);MMP9及其mRNA的表达均与癌组织的浸润深度、分化程度、淋巴结转移密切相关;68例p53表达阳性,阳性率为90.7%,与对照组比较有显著性差异(P<0.05);MMP9表达阳性组的p53阳性例数明显高于MMP9表达阴性组的p53阳性例数,两者之间有显著性差异(P<0.05)。食管癌中MMP9表达与p53表达呈正相关(r=0.652,P<0.01)。84×103(活性形式)和92×103(前酶形式)的MMP9在食管癌组织中的活性明显比癌旁组织和远端食管组织中的强(P<0.05)。结论:食管癌细胞自身具有产生与分泌MMP9的能力,MMP9对肿瘤的浸润、转移具有促进作用。

Objective: To investigate the expression of MMP-9 and MMP-9 mRNA in the tissue and cell of the esophageal carcinoma and its correlation with invasion,metastasis and p53 of the cancer. Methods: Immunohistochemistry,in situ hybridization,and zymography were used to examine the expression of MMP-9,MMP-9 mRNA,p53. The relationship between the expression of MMP-9 and MMP-9 mRNA and the clinical parameters was analyzed. Results: The positive rate of MMP-9 expression was 82.7% in esophageal carcinoma tissues(62/75). The positive rate of MMP-9 mRNA expression was 72.0% in the esophageal carcinoma tissues(54/75). Compared with normal tissue, it showed obvious difference (P<0.01). The expressions of MMP-9 and its mRNA were closely related to invasion,differentiation and lymph nodes status of the esophageal carcinoma. The positive rate of p53 expression was 90.7% (68/75). Compared with normal tissue, it showed significant difference (P<0.05). There was statistically significant defference between p53-positive cases of the MMP-9 positive group and p53-positive cases of the MMP-9 negative group(P<0.05). There was a positive correlation between the MMP-9 expression and the p53 expression in esophageal carcinoma(r=0.652,P<0.01). The various forms of MMP-9(dimeric form-130×10~3,pro-MMP-9-92×10~3 and active-MMP-9-84×10~3) were found in mucosa of surgical up-edge,paracancerous mucoas and cancer lesions. Activity of active-MMP-9 and pro-MMP-9 was significantly higher in the cancer lesions than in the paracancerous mucosa and the mucosa of surgical up-edge. Conclusion: Esophageal cancer cells have the ability to produce and secret MMP-9 which can promote the invasion and metastasis of the neoplasm.