肺癌前病变、肺癌中FHIT基因表达的临床研究  

Expression of FHIT Gene in Precancerous Lesions and Primary Lung Cancer Tissues

作　　者：常秀军[1] 杨声[1] 张海青[2] 汪蕙[3] 姜颖[2] 

机构地区：[1]北京市结核病胸部肿瘤研究所胸外科 [2]北京市结核病胸部肿瘤研究所病理科 [3]北京市结核病胸部肿瘤研究所肺癌分子生物研究室

出　　处：《结核病与胸部肿瘤》2007年第3期197-203,共7页Tuberculosis and Thoracic Tumor

摘　　要：背景与目的FHIT基因为近年发现的新候选抑癌基因，位于3P14．2跨越FRA3B易脆点，在包括肺癌在内的人类多种肿瘤中均存在异常表达。本研究旨在观察FHIT基因在人肺癌前病变、肺癌中表达情况，探讨FHIT基因在人肺癌发生、发展过程中的可能作用。方法采用免疫组化方法检测298例甲醛固定、石蜡包埋的标本（包括161例肺癌、51例肺癌前病变、30例正常肺组织、23例肺良性病变和33例肺癌转移淋巴结）中FHIT蛋白表达情况。结果FHIT蛋白在正常肺组织及肺良性病变组织中均无失表达；癌前病变组织及肺癌组织中失表达率分别为54．9％（28／51）和59．0％（95／161）：肺癌转移淋巴结组织中FHIT蛋白失表达率78．8％（26／33），各组问比较有显著性差异（P〈0．05）。肺癌组织中FHIT基因表达水平与肺癌组织学类型、肿瘤细胞分化程度、患者P-TNM分期、淋巴结转移程度存在相关性（P〈0．05）。FHIT蛋白失表达组肺癌患者的术后五年生存率显著低于表达组（P〈0．01）。吸烟组患者FHIT基因失表达率69．1％（94／136）显著高于无吸烟组49．5％（49／99）（P〈0．01）。结论FHIT蛋白失表达可能是肺癌发生过程中的早期分子事件，与肺癌的发生、发展及预后有关；吸烟导致FHIT蛋白表达下降可能是诱发肺癌的原因之一。Background and Objective Fragile histidine triad （FH1T） gene, a candidate tumor-suppressor gene, is recently identified at chromosome 3p14.2, spanning the FRA3B common fragile site. Abnormalities in the expression of FHIT gene have been reported in a variety of human tumours, including lung cancer. The aim of this study is to investigate the expression of FHIT gene in precancerous lesions and primary lung cancer and analyze the role of FHIT gene in lung tumorigenesis. Methods FHIT protein expression was detected in 298 cases of formalin fixed Paraffin-embeded human samples as controlled by immunohistochemistry, including 51 precancerous lesions,161 lung cancer samples,53 normal lung tissue samples and benign pulmonary lesion tissues, 33 metastatic lymph nodes. Results All the normal lung tissues and pulmonary benign lesions showed positive FHIT protein expression, while the negative rate of FHIT protein expression in precancerous lesions,lung cancer tissues and metastatic lymph node was 54.9% ,59% and 78.8% respectively. Negative rate of FHIT protein in metastatic lymph nodes, lung cancer tissues and precancerous lesions was significantly higher than that in normal lung tissues and benign lesions （P〈 0.001）.The expression of FHIT gene was closely related to histological classification, cell differentiation, pTNM stages and lymph node metastasis in lung cancer （P〈0.05）. A marked reduction of FHIT protein expression was observed in patients with smoking history than that in patients without smoking history （P〈0.01）. Furthermore, FHIT protein expressing level in lung cancer was associated with survival of patients （P〈0.01）. Conclusion These results suggest that FHIT protein expression may occur, at early stage of lung carcinogenesis and be associated with the oncogenesis and progression of cancer. The correlation between cigarette smoking and FHIT expression suggests a role of FHIT in the initiation of smoking - related tumorigenesis.

关 键 词：肺癌前病变 肺肿瘤 FHIT基因 免疫组织化学 

分 类 号：R734.2[医药卫生—肿瘤]