应用组织芯片研究肺癌及癌前病变组织中FHIT的表达及其意义

The biological significance of FHIT protein expression in lung cancer and precancerous tissues detected by tissue microarray

背景与目的脆性组氨酸三联体(fragile histidine triad,FHIT)是候选抑癌基因,在多种与环境致癌物有关的恶性肿瘤中常有FHIT的改变。本研究利用组织芯片技术检测FHIT在不同进展阶段肺癌中的表达,探讨其在肺癌发生、发展中的作用和意义。方法应用免疫组织化学SP法检测270点组织芯片中FHIT蛋白的表达,其中原发肺癌89例、淋巴结转移性肺癌12例以及肺癌癌前病变12例,并结合肺癌的临床病理特征进行分析。结果FHIT蛋白阳性产物主要定位于胞浆。在原发性肺癌、癌前病变组织和淋巴结转移癌组织中FHIT表达缺失率分别为46.1%、41.7%和50.0%,而在10例正常肺组织中FHIT均有表达。原发性肺癌组、癌前病变组和转移癌组FHIT蛋白的表达缺失率均高于正常组(P<0.05);原发癌与转移癌、原发癌与癌前病变、癌前病变与转移癌之间FHIT表达差别无统计学意义(P>0.05),且FHIT表达缺失与肺癌组织学类型、分化程度以及患者的吸烟史相关且有统计学意义(P<0.05),而与性别、年龄、临床分期、是否伴有淋巴结转移以及肉眼类型无关(P>0.05)。结论FHIT在肺癌和癌前病变中表达下降,尤其在鳞癌、低分化组和吸烟病例中表达缺失率高,FHIT表达缺失可能与肺癌早期发生、发展及吸烟致癌过程有密切的关系。

Backgroud and objective Fragile histidine triad (FHIT) is a candidate tumor suppressor gene. Aberrant expression of FHIT has been observed in multiple carcinomas induced by environmental carcinogens, especially in lung cancer. In this study, the expression of FHIT protein in lung cancer progression tissue microarray was detected and their roles in oncogenesis and progression of lung cancer were discussed. Methods The expression of FHIT protein in tissue microarray with 270 cores was detected by SP immunohistochemistry method, in which there were 89 cases of primary lung cancer, 12 cases of lymph node metastasis of lung cancer, 12 cases of precancerous lesion and 10 cases of normal lung tissue, and the clinicopathological features of lung cancer were analyzed. Results The expression of FHIT was localized in the cytoplasm. Loss of FHIT expression in primary cancers, precancerous lesion and lymph node metastasis of lung cancer was 46.1%, 41.7% and 50.0% respectively, while 0 in 10 cases of normal tissues. A significant difference of FHIT expression was observed among four groups (P<0.05). Loss of FHIT expression in precancerous lesion, primary lung cancer and lymph node metastasis of lung cancer was significantly higher than that in normal lung tissue (P<0.05). The difference among precancerous lesion, primary lung cancer and lymph node metastasis of lung cancer groups was not statistically significant (P>0.05). Loss of FHIT expression was related to tumor histologicol types, degree of cell differentiation and the smoking history of patients (P<0.05), but not to sex, age, gross appearance types, TNM stages, or lymph node metastasis (P>0.05). Conclusion The protein expression level of FHIT is reduced in primary cancers and precancerous tissues, especially in most squamous cell carcinomas, poorly differentiated group and the patients with a smoking history. These results indicate that loss of FHIT expression might correlate with carcinogenesis, development of lung cancer and the carcinogenesis induced by smoking.