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

背景与目的FHIT基因为近年发现的新的候选抑癌基因,位于3p14.2,跨越FRA3B易脆点,在包括肺癌在内的多种人类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、肺癌中的表达情况,探讨FHIT基因在肺癌发生、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,癌前病变组织和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失表达率为78.8%(26/33);肺癌前病变、肺癌及转移淋巴结组织中FHIT蛋白失表达率显著高于正常肺组织及肺良性病变组织(P<0.001)。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pTNM分期、淋巴结转移有密切关系(P<0.05)。FHIT蛋白失表达组肺癌患者的术后5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%显著高于无吸烟组49.5%(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 （FHIT） gene, a candidate tumor suppressor gene, is recently identified at chromosome 3p14.2, spanning the FRA3B common fragile site. Abnormalities in 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 to analyze the role of FHIT gene in lung tumorigenesis. Methods FHIT protein expression was detected in 298 cases of formalin fixed paraffin-embedded human samples by immunohistochemistry, including 51 precancerous lesions, 161 lung cancer samples, 30 normal lung tissue samples, 23 pulmonary benign lesion tissues and 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 nodes was 54.9 ~, 59.0 % 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 pulmonary 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 expression 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 lung tumorigenesis.