P1-107: Evaluation of Simian Virus-40 as a biological prognostic factor in egyptian patients with malignant pleural mesothelioma

Abstract

Malignant Mesothelioma is a highly aggressive primary neoplasm of the pleural, peritoneal, and pericardial surfaces. It is a challenging disease in all aspects, from presentation and diagnosis to staging and treatment. In the past 50 years, the incidence of malignant pleural mesothelioma (MPM) has been increasing especially in developing countries, along with industrial development. The association between simian virus (SV40) and malignant pleural mesothelioma (MPM) suggests an etiological role for SV40. However, exact pathogenic mechanisms and possible prognostic value are not clear. Transformation of human cells by SV40 is induced by the large tumor antigen (Tag) and the small tumor antigen (tag). The main mechanism(s) by which the Tag induces cell transformation and tumorigenesis is via the inactivation of key cellular proteins, such as p53 and pRB family proteins. Fresh tumor tissues were obtained from 40 MPM Egyptian patients presenting at NCI,Cairo. Of them, 22 were from extra-pleural pneumonectomy specimens and 18 from thoracoscopic biopsies. All cases were diagnosed as MPM and graded using World Health Organization (WHO) criteria on hematoxylin and eosin-stained sections combined with immunohistochemistry and clinical features. All cases diagnosed as MPM were positive for mesothelioma markers (calretinine, mesothelioma antigen, keratin 5/6) and negative for epithelial membrane antigen and/or cytokeratin and/or CEA. Sarcomatoid cases were diagnosed by being positive for mesothelioma antigen and negative for vimentin. The samples were also investigated for the presence of SV40 DNA, altered Rb expression and p53 gene status using immunohistochemistry and molecular techniques. Patients were staged according to the International Mesothelioma Interest Group (IMIG) staging system. The relation between SV40, asbestos exposure, Rb, p53 and their contribution to clinicopathologic characteristics and overall survival (OS) were assessed. The age ranged from 20 to 69 years (mean= 45± SD), 21 were males and 19 were females. SV40 DNA was detected in 20/40 cases and asbestos exposure in 31 cases; 18 of them were SV40 positive. Altered p53 and Rb expression were detected in 57.5% and 52.5% respectively with no p53 mutation. There was a statistically significant correlation between the presence of SV40 viral sequences and the pathological type of the tumor since 13 out of the 20 SV40 positive cases (65%) were of the sarcomatoid/mixed variants compared to 7 (35%) of the epithelioid variant (p.= 0.03). Similarly, there was a statistically significant correlation between the presence of SV40 viral sequences and a positive history of asbestos exposure (p. = 0.03). Univariate analysis showed a significant correlation between OS and stage (p= 0.03), performance status (p=0.04), p53 overexpression (p=0.05), asbestos exposure (p=0.002) and SV40 (p=0.001). Multivariate analysis showed that when SV40 and asbestos exposure were considered together, only combined positivity of both is an independent prognostic factor affecting the OS (p = 0.001). SV40 and asbestos exposure are common in Egyptian MPM denoting a possible etiological role and a synergistic effect for both agents. Our results prove that combined positivity for SV40 and asbestos exposure is an independent prognostic factor in MPM having a detrimental effect on OS