HPV感染、FHIT蛋白表达与非小细胞肺癌的相关性研究

RELATIONSHIP AMONG HPV INFECTION,FHIT PROTEIN EXPRESSI ON AND NON-SMALL CELL LUNG CANCER

目的探讨人乳头瘤病毒感染在NSCLC发生中的病因学意义,同时分析FHIT蛋白表达与NSCLC发生及HPV感染的关系。方法采用PCR方法选用通用型引物和HPV16、18型特异性引物分别对42例NSCLC及14例肺良性病变组织进行检测。免疫组化SP法检测FHIT蛋白的表达水平。结果HPVDNA检出率肺癌组为42·9%,肺良性病变组为7·1%,二者有显著性差异(P<0·05)。HPV感染率在肺鳞癌(53·6%)显著高于腺癌(21·4%),且随着分化程度降低,其感染率增高,在吸烟患者(57·7%)显著高于不吸烟患者(18·8%);FHIT蛋白异常表达率肺癌组为61·9%,与肺良性病变组(28·6%)比较有显著性差异(P<0·05)。肺癌中HPV阳性组FHIT蛋白异常表达率为83·3%,明显高于HPV阴性组(45·8%,P<0·05)。结论HPV感染与NSCLC组织学类型、分化程度及吸烟有关,它可能是导致NSCLC发生的重要病因学因素之一;FHIT蛋白异常表达与NSCLC发生及HPV感染有关,HPV可能通过诱导FHIT表达异常参与NSCLC的发生发展过程。

Objective To investigate the etiological role of human papillomavirus （HPV） infection in the carcinogenesis of non-small cell lung cancer （NSCLC） and to elucidate the possible relationship among fragile histidine triad protein （FHIT） expression and carcinogenesis of NSCLC and HPV infection. Methods 42 cases of NSCLC and 14 cases of benign lung diseases were respectively examined with general polymerase chain reaction （PCR） to detect the HPV positive rate by type consensus primers and the HPV16 and 18 type-specific primers. The FHIT protein expression levels in NSCLC were detected by SP immunohistochemistry. Results The detection rate of HPV DNA was 42. 9 % in the lung cancer group and 7. 1% in the benign diseases group, with a significant difference between the two groups （P〈0. 05 ）. The HPV infection rate in squamous cell carcinoma （53. 6%） was significantly higher than that in adenocarcinoma （21.4%）, and it increased with the decrease in the degree of carcinoma differentiation. The HPV infection rate in smoking lung cancer patients （57.7%） was significantly higher than that in non-smokers （18.8%）. Immunohistochemically, the aberrant expression rate of FHIT protein was 61.9% in lung cancer, significantly higher than that in benign diseases （28. 6%, P〈0. 05 ）, and it was significantly higher in HPV DNA positive 83.3% than in HPV DNA negative lung cancer cases （45.8%, P〈0. 05）. Conclusion There is a relationship between HPV infection and histological classification of NSCLC, degree of carcinoma differentiation and smoking. The infection may be one of the important etiological factors in the carcinogenesis of NSCLC. The aberrant expression of FHIT is correlated with the carcinogenesis of NSCLC and HPV infection. HPV may participate in the carcinogenesis and development of NSCLC by inducing FHIT aberrant expression.