HPV感染与p53蛋白及P-糖蛋白表达在非小细胞肺癌中的关系及其临床意义

Relationship between human papillomavirus infection and the expressions of p53 and P-glycoprotein in non-small cell lung cancer and its clinical significance

目的:探讨人乳头瘤病毒(humanpapillomavirus,HPV)感染在非小细胞肺癌(nonsmallcelllungcancer,NSCLC)发生中的病因学意义及其与p53蛋白和P糖蛋白(Pgp)表达之间的相关性。方法:应用PCR、免疫组化方法分别检测76例NSCLC组织中HPVDNA及其E6、E7原癌蛋白、p53蛋白和Pgp的表达情况。结果:NSCLC中HPVDNA及其E6、E7原癌蛋白的检出率分别为40.8%(31/76)、43.4%(33/76),2种检测方法的符合率为78.9%(60/76);p53蛋白和Pgp的阳性率分别为63.2%(48/76)、59.2%(45/76),且HPV感染阳性组中p53蛋白的表达率为80.6%(25/31),显著高于阴性组51.1%(23/45)(P<0.05);p53蛋白表达阳性组中Pgp的表达率为68.8%(33/48),显著高于阴性组42.9%(12/28)(P<0.05);而HPV感染阳性组与阴性组间Pgp的表达无显著性差异(P>0.05)。HPV感染与高、中分化程度的NSCLC及吸烟有关。结论:HPV感染可能是NSCLC发生的另一重要病因学因素,且HPV感染可能导致p53基因突变,后者可能促进肺癌耐药性的增加。

Objeetive：To investigate the etiological significance of human papillomavirus （HPV） infection in non-small cell lung cancer （NSCLC） and its association with the expressions of p53 and P-glycoprotein （P-gp）. Methods：Polymerase chain reaction （PCR） and SP immunohistochemical （IHC） methods were used to detect the expressions of HPV DNA and its E6 and E7 oncoproteins, p53, and P-gp in 76 cases of NSCLC, respectively. Results： The positive rates of HPV DNA, HPV E6 and E7 oncoproteins in 76 cases of NSCLC were 40.8% （31/76） and 43.4% （33/76）,respectively. The coincident rate between PCR and IHC was 78.9% （60/76）. The positive rates of p53 and P-gp were 63.2% （48/76） and 59.2% （45/76）, respectively. The positive expression of p53 （80. 6%, 25/31） was significantly higher in the HPV-positive group than that in HPV-negative group （51.1%, 23/45, P〈0.05）. The positive expression of P-gp（68.8%, 33/48） was significantly higher in p53-positive group than that in p53-negative group （42.9%, 12/28, P〈0.05）. There was no significant difference in P-gp expression between HPV-positive and HPV-negative group（P〉0.05）. The HPV infection was significantly correlated with highly and moderately differentiated NSCLC and smoking. Conclusion： HPV infection may be one of etiological factors in the occurrence of NSCLC. HPV infection may induce the mutation of p53. Mutation of p53 may increase the multidrug resistance of the lung cancer.