【摘要】 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。更多还原

【Abstract】 BACKGROUND &OBJECTIVE:Abnormality of FHIT g ene has been proved to be frequent in certain malig nant tumors closely related to environmental oncog enic factors ,s uch as lung cancer.Foreig n scholars have beg un to explore the relationship be tween FHIT g ene and other tumor suppr essor g enes ,which are implicated in the pa thog enesis of lung cancer.This stud y was desig ned to investig ate the relatio nship between hMSH 2 and FHIT protein expression and to explore the correl ation of hMSH 2 and FHIT protein expression with clinicopatholog ic features of lung cancer.METHODS :Immunohistochemical analysis of hMSH 2 and FHIT protein expression in 40lung cancer cases and 15adjacent non-cancer lung tissues wa s performed;the positive rates of FH IT and hMSH 2 proteins were measured by imag e anal ysis system.RESULTS :(1)The positive rates of FHIT and hMSH 2 proteins were 58.2%and 45.8%respec tively in lung cancer tissues compared with89.1%and 65.3%in non-cancer lung tissues.The expression levels of FH IT and hMSH 2 proteins were sig nificantly lower in lung cancer tissues than tha t in non-cancer lung tissues (P<0.01).(2)Reduced expression levels of both pr oteins were sig nificantly related t o tumor histolog y.The positive rate of the F HIT protein was 52.2%in squamous cel l carcinoma compared with 63.4%in ade nocarcinomas (P<0.01),whereas the positive rate of the hMSH 2 protein was 35.6%in adenocarcinoma s compared with 53.2%in squamous cell carcinom a(P<0.01).(3)A correlation between FHIT reduced expression and lymph node metastasis was observed(P<0.01).The positive rate of the FHIT protein was 54.1%in lung cancer tissues with metastasis compared with 60.5%in lu ng cancer tissues without metastasi s.No association was found between hMSH 2 reduced expression and nodal metast asis(P>0.05).(4)Loss of FHIT protein correlated sig nificantly with lasting and heavy smoking(P<0.01).The positive rate of the FHIT protei n was 53.1%in smoking g roup compared with 66.1%in non-smoking g roup.The reduction of hMSH 2 expression was not associated with s moking(P>0.05).(5)An inverse correlation was found between hMSH 2 reduced expression and FHIT protein loss(P<0.01,RR =-0.54).CONCLUSION:FHIT g ene may be a neg ative reg ulatory g ene of hMSH 2 g ene,and play an important role in th e inactivation mechanism of hMSH 2 g ene.更多还原