胃癌中hMSH2和PTEN的表达及临床意义

摘要

目的：探讨人类 mut-s同系物2（human mut-s homologue 2，hMSH2）和抑癌基因人第10号染色体缺失的磷酸酶及张力蛋白同源的基因（gene of phosphate and tension homology deleted on chromosome ten，PTEN）在胃癌组织中的蛋白表达及与临床病理特征之间的关系。方法采用 SP 免疫组织化学法检测42例胃癌组织及其相应的近端癌旁组织（距癌组织3cm）、远端癌旁组织（距癌组织＞10cm）及15例正常胃组织 hMSH2和 PTEN蛋白表达；采用Western Blot半定量检测42例胃癌组织及相应远端癌旁组织（距癌组织＞10cm）hMSH2和PTEN蛋白表达。分析 hMSH2和PTEN在胃癌组织中的蛋白表达与临床病理特征之间的关系。结果胃癌组织中 hMSH2和PTEN蛋白表达缺失率明显高于近端癌旁组织、远端癌旁组织及正常胃组织（P＜0．05或＜0．01）。PTEN蛋白表达缺失率与肿瘤分化程度负相关（rs＝-0．707，P＜0．05），与 TNM分期、浸润深度、淋巴结转移呈正相关（rs＝0．748、0．979、0．850、0．877，P＜0.05）。hMSH2和PTEN蛋白表达在胃癌中呈正相关。在胃癌组织中错配修复基因 hMSH2蛋白表达缺失伴有PTEN蛋白表达下调。结论 PTEN表达与胃癌临床病理特征相关；在胃癌发生发展过程中错配修复蛋白 hMSH2表达缺失伴有PTEN蛋白表达下调。%Objective To investigate the expression of human mut-s homologue 2 (hMSH2)and phosphatase and tensin homology deleted on chromosome ten (PTEN)in sporadic gastric carcinoma,and thereby to elucidate their relationship and clinical significance.Methods The expression levels of hMSH2 and PTEN were detected using immunohistochemistry in 42 cases with sporadic gastric carcinoma,its corresponding adjacent tissues (3cm away from cancerous tissues),distal tissues (from cancer>10cm)and 15 cases of normal gastric tissues.The expression levels of hMSH2 and PTEN protein were analyzed using Western Blot in 42 patients with sporadic gastric carcinoma and its corresponding distal controls.Results Loss rate of expression of hMSH2 and PTEN in gastric cancer were higher than that of proximal tumor-adj acent gastric carcinoma tissues,distal tumor-adj acent gastric carcinoma tissues and normal gastric tissues (P<0.05 or P<0.01).PTEN loss rate showed negative correlation with the degree of tumor differentiation (rs=-0.707,P<0.05),but positive correlation with TNM staging, invasive depth,and lymph node metastasis (P<0.05).hMSH2 and PTEN were positive correlated in gastric cancer.There was a decreasing expression in expression losses of mismatch repair gene and hMSH2.Conclusion PTEN protein expression is correlated with clinic and pathological features.The expression deletion of mismatch repair protein hMSH2 was accompanied by down-regulated PTEN protein expression in sporadic gastric carcinoma.