The Relationship Among Human Papillomavirus Infection And The Expression Of Protein P53 And P-gp In Non-small Cell Lung

Objective: 1. To investigate the etiological role of HPV on the carcinogenesis of NSCLC.2. To detect the relationship among HPV infection and the expression of protein p53 and P-gp, and to investigate the possible relationship between HPV and the multidrug resistance of clinical chemotherapy.3. To demonstrate the relationship between HPV infection,the expression of p53 protein,P-gp in the NSCLC and clinical pathological characteristics.Methods: 76 cases of NSCLC and 13 cases of lung benign diseases were respectively examined by PCR with the HPV16,18 type-specific primers. S-P immunohisto- chemical (IHC) methods were used to detect the expression of HPV E6,E7 protein,p53 protein and P-gp in 76 cases with NSCLC.Results: 1. To detect HPV DNA and the expression of HPV E6,E7 protein in NSCLCThe percentage of positive of HPV DNA in 76 cases of NSCLC was 40.8%(31/76) and that in 13 cases of lung benign diseases was 7.7%(1/13).There was a significant difference between the two groups( P <0.05 ). The percentage of expression of HPV E6,E7 protein was 43.4%(33/76),and the coincident rate of PCR and IHC was 78.9%.2. To detect the relationship among HPV infection and the expression of protein p53 and P-gp in NSCLCOf 76 NSCLC,the percentage of positive of protein p53 was 63.2 %(48/76), and it was evidently higher in the positive group of HPV infection (80.6%)(25/31) than it in the negative group (51.1%)(23/45) (P<0.05);Of 76 NSCLC,the percentage of positive of P-gp was 59.2%(45/76), and it was significantly higher in the positive group of p53(68.8%)(33/48) than it in the negative group(42.9%)(12/28) (P<0.05);Otherwise the percentage of positive of P-gp was no evident difference between HPV DNA positive(71.0%)(22/31)and negative (51.1%)(23/45)(P>0.05);and it was no evident difference between HPV DNA positive,p53 positive(55.0%)(11/20)and HPV DNA negative,p53 positive(46.4%) (13/28) (P>0.05).3. The relationship between HPV infection,expression of protein p53,P-gp and clinicopathological characteristics in NSCLCHPV infection frequently happened in highly or moderately differentiated NSCLC, and the rate was 60.0%(9/15) and 53.3%(16/30) respectively, which was obviously higher than that in poorly differentiated NSCLC(19.4%)(6/31)(P<0.05). Moreover HPV infection rate in smoking lung cancer patients(52.0%)(26/50)was significantly higher than that in non-smokers(19.2%)(5/26)(P<0.05)in 76 cases of NSCLC. However No correlation was found between HPV infection rand age,sex,histological type,lymph node metastasis as well as clinical stage of the patients. p53 had obvious difference between squamous cell carcinoma(85.4%)(35/41) and adenocarcinoma (37.1%)(13/35)of NSCLC(P<0.05). P-gp was significant higher in the high(86.7%)(13/15)and middle(63.3%)(19/30) degree of carcinoma differentiation of NSCLC than it in the low(38.7%)(13/31)(P<0.05).Conclusion: 1. The percentage of positive of HPV DNA in 76 cases of NSCLC is much higher than that in benign diseases, which strongly suggests that HPV infection may be another important etiological factor that results in the occurrence of NSCLC.2. The percentage of expression of p53 was evidently higher in the positive group of HPV infection than in the negative group, which illustrated that HPV infection also may induce the gene of p53 to mutate; The percentage of expression of P-gp was significantly higher in the positive group of p53 than in the negative group, which indicated that the mutation of p53 may increase the multidrug resistance of the lung cancer; However there was no evident relationship between P-gp and HPV, which suggested that HPV infection can not increase the multidrug resistance directly, and can not influence the multidrug resistance by the mutation of p53.3. HPV infection was significantly correlated with the high and middle degree of carcinoma differentiation of NSCLC and smoking, which indicated that the replication of virus required some differentiation and there was synergism between HPV infection and smoking. The expression of p53 was significantly correlated with the histological type of NSCLC, which suggested that the mutation of p53 was prone to occur in Squamous cell carcinoma. The expression of P-gp was significantly correlated with the high and middle degree of NSCLC, which proved that the low malignant carcinoma desensitized with chemotherapy.