Expression Of Epidermal Growth Factor Receptor, P53, MDM2 And Their Correlation With HPV Infection In Vulvar Intraepithelial Neoplasia And Vulvar Carcinoma

Epidermal growth factor (EOF) is an important regulatory factor of cell growth, it can stimulates cell mitosis, proliferation and differentiation, Its binding to the receptor modulates cells growth and normal cells malignant transformation. Epidermal growth factor receptor (EGFR) is a single chain polypeptide, which expresses by c-erB-1 gene and has a molecular weight of 170KDa. EGFR has the action of tyrosin kinase. EGFR can stimulates cells growth when it is normal expression, but it also can stimulates normal cells malignant transformation when it is overexpression. There is a positive relationship between EGFR overexpression and neoplasm formation.The P53 tumour suppressor gene encodes phosphoprotein with an apparent molecular mass of 53KDa, which has two types, namely wild-type P53 protein (wt-P53) and mutation P53 protein (mt-P53). The P53 gene encodes transcriptional factor central in the regulation of cell growth, DNA repair, apoptosis induction. The structure of P53 protein takes transformation when the P53 gene mutates, which is more stable than wt protein and can accumulate in the cell.There different mechanisms may explain the loss of P53 function ?a somatic gene mutation which leads to an inactive form, the mdm2 (murine double minute-2) gene product, a 90 KDa protein , can bind to wt and mutant P53 , and overexpression of mdm2 inhibits the function of P53 ,and the enhanced protein degradation promoted by the E6 oncoprotein of the human papilloma virus types (HPV) 16 and 18. There is a DNA position which likes P53 in the first intron of MDM2, and these is the basic structure of the MDM2 gene regulating the P53 gene. The P53 function is inactive when the MDM2 protein combines the P53 protein, On the other hand, it can stimulate the answer of the P53 element when the MDM2 protein combines the P53 protein, which it can induce the transcriptional function of the MDM2 gene, and regulate the function of the MDM2 gene. In this way, the MDM2 gene forms an autoregulatory feedback loop with P53.One-third of vulvar carcinoma are related with HPV infection. There are over 130 subtypes in HPV , which is a group of high distinctive DNA virus. The structure of HPV genes are almost similar, which has three sections, namely late area ,early area , regulating area. There are six open reading frames .The E5 gene is related with cell membrane receptor, but E6 and E7 genes are related with the changing of cells function and cells malignant transformation .HPV can divided into a high risk type and a low risk type according to the cells function of transformation. The low risk type HPV 6/11, it's E6 and E7 genes are lack of the cells function of transformation, can lead to benign proliferation such as papilloma and condyloma. The E6 and E7 genes of high risk type HPV 16718 can lead to cells malignant transformation through their E6 and E7 protein binding to P53 and retinoblastom protein respectively .The late studies proved that the inactivation of suppressor gene, the expression of oncogene and virus genes are closely related with the cells proliferation, and the overexpression of these production of genes are also with the development of carcinoma.Up to now, there is no report about expression of EGFR, P53, MDM2 and their correlation with HPV infection in vulvar intraepithelial neoplasia andvulvar carcinoma.In this study, we have detected the infection of HPV 6/1 land HPVI6/18 in vulvar intraepithelial neoplasia (VIN), vulvar cancer and the nomal vulvar skin epithelium with in site hybridization method in order to make clear the role that the infection of HPV in vulvar cancer. In the meanwhile , we have detected the expression of EGFR, P53 and MDM2 in vulvar dystrophies, VIN, vulvar cancer , adjacent tissues of cancer and the nomal vulvar skin epithelium immunohistochemically in order to elucidate the role that the overexpression of EGFR, P53 or MDM2 playing in early carcinogensis and progress of vulvar carcinoma. We also make clear the relationship between P53 and MDM2, HPV and EGFR, HPV and P53...