Expression of HPV E7 Protein in Cervical Cancer and Cervical Intraepithelial Neoplasia and Its Correlation to Other Parameters

Less than 10% of women with atypical squamous cells of undetermined significance (ASCUS) or above in their Papanicolaou smear show histological cervical intraepithelial neoplasia grade 2 (CIN 2) or more severe lesions. There are also less than 10% of women with positive high-risk human papillomavirus DNA showing histologic CIN 2 or above in the cervix. For the great majority of women with abnormal smear or HPV DNA positive, there is no detectable cellular transformation; It can only be followed until the abnormality resolves spontaneously, or a detectable lesion appears. Up to date, clinical tools that could directly explain the causes of abnormal smear have not yet been found; concerning mild abnormality, especially, direct measures to indicate the HPV infected cells and the consequent change after infection have not yet been found, either. Even though p16INK4a, an indirect indicator of HPV infection, appears after the degradation of pRb caused by HPV E7 protein theoretically, the specificity of p16INK4a staining is not perfect since nondysplastic cervical cells, some endometrial carcinoma and ovarian cancer also show diffuse p16INK4a positive. In order to tackle this issue, we have developed some polyclonal rabbit antibodies and monoclonal mouse antibodies against E6/E7 oncogenes. A representative monoclonal antibody against HPV 16 E7 oncoprotein was selected as a good candidate for further investigation. Immunohistochemical and immunocytochemical staining showed that the antibody marked transformed cells in CIN and in invasive cervical cancer cells as well. Moreover, it also showed a stepwise increase in cytoplasmic expressions ranging from almost no expression in CIN 1, 38% in CIN 2, 52% in CIN 3, 97% in adenocarcinoma and 100% in squamous cell carcinoma on histochemical staining. This novel finding encourages us to undertake further research on: (1) The discovery of the differences of E7 expression in different stages of HPV infection and cell transformation in different infected HPV types; (2) the correlation between the E7 expression and HPV DNA integration in clinical specimens; (3) the investigation into the clinical utility of E7 immunohistochemistry and immunocytochemistry, and the comparison of its efficacy with p16INK4a staining in women with abnormal Papanicolaou smear (ASCUS or above); and (4) the discovery of the interaction of E7 related protein in clinical samples with different stages of HPV infection/transformation, by means of Quantum Dot immunofluorescent staining

Project ID:PC9808-0571
External Project ID:NSC98-2314-B182-047-MY3