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背景与目的:有研究表明脆性组氨酸三联体(fragilehistidinetriad,FHIT)基因在与环境致癌因素关系密切的恶性肿瘤(如肺癌)中表达异常率较高。本研究旨在分析肺癌组织中hMSH2基因与FHIT基因表达的相关性,并探讨FHIT、hMSH2基因表达下降与肺癌临床病理特征的关系。方法:应用免疫组化法检测40例肺癌组织和15例癌旁非癌肺组织中FHIT及hMSH2基因的表达水平,用图像分析系统测量FHIT、hMSH2蛋白表达的阳性率。结果:(1)肺癌组织中FHIT、hMSH2蛋白表达阳性率分别为58.2%、45.8%,显著低于非癌肺组织的89.1%、65.3%(P<0.01);(2)鳞癌中FHIT蛋白表达阳性率(52.2%)低于腺癌(63.4%),而腺癌中hMSH蛋白表达阳性率(35.6%)低于鳞癌(53.2%),其差异均有显著性(P<0.01);(3)有淋巴结转移的肺癌组织FHIT蛋白表达阳性率(54.1%)低于未发现淋巴结转移的肺癌组织(60.5%)(P<0.01),而hMSH2蛋白表达阳性率在两组患者中的差异无显著性(P>0.05);(4)吸烟组中FHIT蛋白表达阳性率(53.1%)低于不吸烟组(66.1%)(P<0.01),hMSH蛋白表达阳性率在两组间的差异无显著性(P>0.05);(5)FHIT基因表达阳性率与hMSH2基因表达强度呈负相关(P<0.01,RR=-0.54)。结论:FHIT基因可能为hMSH2的负调节基因,在hMSH2失活机制中起重要作用。
BACKGROUND & OBJECTIVE: Some studies have shown that the abnormal expression rate of fragile histidine triad (FHIT) gene in malignant tumors (such as lung cancer) is closely related to environmental carcinogens. This study aimed to analyze the correlation between hMSH2 gene and FHIT gene expression in lung cancer and to explore the relationship between the decrease of FHIT and hMSH2 gene expression and clinicopathological characteristics of lung cancer. Methods: The expression of FHIT and hMSH2 genes were detected by immunohistochemistry in 40 lung cancer tissues and 15 non-cancerous non-cancerous tissues. The positive rate of FHIT and hMSH2 protein expression was measured by image analysis system. Results: (1) The positive rates of FHIT and hMSH2 in lung cancer were 58.2% and 45.8%, respectively, which were significantly lower than those in non-cancerous lung tissues (89.1% and 65.3%, P <0.01) (52.2%) was lower than that of adenocarcinoma (63.4%). The positive rate of hMSH protein in adenocarcinoma was lower than that in squamous cell carcinoma (35.6% vs 53.2%, P <0.01). (3) The positive expression rate of FHIT protein in lung cancer with lymph node metastasis (54.1%) was lower than that in lung cancer without lymph node metastasis (60.5%) (P <0.01), while the positive rate of hMSH2 protein expression in the two groups was significantly different (P> 0.05). (4) The positive expression rate of FHIT protein in smoking group (53.1%) was lower than that in non-smoking group (66.1%) (P <0.01) (P> 0.05). (5) The positive rate of FHIT gene expression was negatively correlated with the expression of hMSH2 gene (P <0.01, RR = -0.54). Conclusion: The FHIT gene may be a negative regulator of hMSH2, which plays an important role in the mechanism of hMSH2 inactivation.