Association of Human Papilloma Virus-16 and P53 protein overexpression in malignant surface epithelial ovarian tumors

Human papillomaviruses (HPV) belong to papillomaviridae family that has a particular tropism for the epithelium inducing its proliferation. It has been shown that E6 and E7 protein is capable of binding and inactivating the P53 and Retinoblastoma (Rb) tumor suppressor genes respectively. These interactions are responsible for the transforming activity of HPV. The role of HPV infection in etiology of ovarian cancer remains unclear and the results are controversial. Several studies have verified the presence of HPV DNA in both benign and malignant ovarian tissues. Therefore, it is not surprising that there is considerable interest in the role of HPV in ovarian carcinoma. Objectives of the study 1. Determine the role of E6 protein of HPV16 in pathogenesis of surface epithelial ovarian carcinoma. 2.Determine the role of p53 protein in the pathogenesis of the surface epithelial ovarian carcinoma. 3The correlation between E6 protein of HPV16 and p53 protein in patient with ovarian lesions. Materials and Methods This study was designed as a retrospective one. It involved 61 cases formalin fixed, paraffin embedded ovarian tissue blocks including 35 cases of surface epithelial ovarian tumors (31 cases of invasive surface epithelial ovarian tumors, & 4 cases of borderline intermediate malignancy cases of neoplastic ovarian cystic lesions), 18 blocks of benign epithelial ovarian tumors, and 8 blocks of normal ovarian tissues as a control. The age of those cases range from 20 to 72 years old. Specimens were collected from Al-Baraa private laboratory in Baghdad belong to the period from June 2011 to March 2012. The practical part of this study performed as following: 1.Tissue sectioning and preparation on one ordinary slide, and two positively charge slides. 2.For definitive diagnosis sections one ordinary slide were stained by heamatoxyline- eosin stain. 3. Immunohistochemical technique was used to demonstrate the over-expression state of p53 tumor suppressor gene, and to detect the E6 protein of HPV16. Results 1.The most common histological types of surface epithelial ovarian carcinoma among this study were serous type (83.87%) followed by mucinous type (6.45%). 2.The age of study groups range from 20 to 72 years old, surface epithelial ovarian carcinoma was increased with age, the mean age was (50.06) years while the benign tumor was decreased with age, which was 39% in (20-29) years followed by 36% in (30-39) years, the mean age was (31.44+1.96) years. 3.The High risk type- HPV 16- E6 protein signal was detected in (9.67%) of malignant cases. 4. Over expression of tumor suppressor gene (P53) was detected by IHC in 100% of malignant group and 0% of benign group. Significant difference was found among study groups and according to signal score and intensity. 5.No significant differences were found between over expression of P53 protein and the presence of HPV16 E6 among all study groups.
Conclusions . The study results are consistent with previous studies which appears that HPV infection may plays a limited role in the pathogenesis of ovarian carcinomas or it could facilitate its progression. 6.The most common histological types of surface epithelial ovarian carcinoma among Iraqi patients were serous type (83.87%) followed by endomateriod type (9.68%). 7.The age of study groups range from 20 to 72 years old, surface epithelial ovarian carcinoma was increased with age .the mean age was 50.06 years, while the benign tumor was decreased with age, the mean age was 31.44years. 8.Low percentage of HPV16 was found in high intensity (9.67%) of malignant group. 9.Over expression of P53 was detected by IHC in 100% of malignant group and 0% of benign group. Significant difference was found among study groups and according to signal score and intensity. 10.No Significant difference was found between the presence of P53 and E6 protein of HPV16, among all study groups .