Evaluation of simian virus-40 as a biological prognostic factor in Egyptian patients with malignant pleural mesothelioma

Our plain-English summary of Evaluation of simian virus-40 as a biological prognostic factor in Egyptian patients with malignant pleural mesothelioma, by A.R. Zekri, A.A. Bahnassy, W.S. Mohamed, et al (Pathology International, 2007).

The study

• Authors: A.R. Zekri, A.A. Bahnassy, W.S. Mohamed, N. Hassan, A.R. Abdel-Rahman, F.A. El-Kassem, R. Gaafar
• Journal: Pathology International
• Published: 2007;57(8):493-501
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The association between simian virus (SV40) and malignant pleural mesothelioma (MPM) suggests an etiological role for SV40. However, exact pathogenetic mechanisms and possible prognostic value are not clear. The purpose of the present paper was to investigate 40 Egyptian MPM patients for the presence of SV40 DNA, altered Rb expression and p53 gene status using immunohistochemistry and molecular techniques. The relation between SV40, asbestos exposure, Rb, p53 and their contribution to the overall survival (OS) were also assessed. SV40 DNA was detected in 20/40 patients and asbestos exposure in 31 patients; 18 of them were SV40 positive. Altered p53 and Rb expression were detected in 57.5% and 52.5%, respectively, with no p53 mutation. 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 was 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. Combined positivity for SV40 and asbestos exposure is an independent prognostic factor in MPM, having a detrimental effect on OS.

In plain English

This prospective study in Cairo tested tumors from 40 Egyptian patients with malignant pleural mesothelioma (2001 to 2002) for simian virus 40 (SV40) DNA and for changes in the proteins p53 and Rb. All patients worked or lived near areas known to use asbestos; 31 had a positive exposure history and 9 a negative one. SV40 DNA was found in 20 tumors, 18 of them from history-positive patients. Tumors showed p53 overexpression in 23 patients, with no mutation in the p53 regions tested (exons 5 to 9), and altered Rb in 21. Median survival was 25.00 months (95% CI 10.21 to 39.79) with SV40 and 47.08 months (42.89 to 51.27) without. It was 32.08 months (21.85 to 42.32) for history-positive patients and 47.08 months (printed as 47.08 to 47.08) for history-negative patients. All 18 double-positive patients died during follow-up. The authors ran a Cox regression that included SV40, asbestos history and their combination, and only the combination was independent. They called its figure of 5.7 (95% CI 2.1 to 15.5) 'odds of death', though that method gives hazard ratios. The authors concluded that SV40 and asbestos both contribute to mesothelioma in these patients.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: prospective study of tumor tissue (laboratory testing plus survival analysis)
• Who was studied: 40 patients with malignant pleural mesothelioma at the National Cancer Institute, Cairo University, Egypt, March 2001 to December 2002. Patients were aged 20 to 69, with 21 male and 19 female. Tissue came from 22 extrapleural pneumonectomy specimens and 18 thoracoscopic biopsies.
• Exposure: History of asbestos exposure was taken during history taking; no fiber type was given. All patients worked in or lived near industrial areas known to use asbestos fibers. Patients were classed as history-positive (31) or history-negative (9). SV40 DNA in the tumor was also studied.
• Main results:
  • SV40 DNA was found in the tumors of 20 of 40 patients (50%)
  • 18 of the 20 SV40-positive patients (90%) had a history of asbestos exposure (P = 0.03 in the text)
  • 13 of the 20 SV40-positive cases (65%) were sarcomatoid/mixed type, compared with 7 (35%) epithelioid (P = 0.03)
  • p53 protein overexpression was found in 23 of 40 patients (57.5%). No p53 mutation was found in the exons studied (exons 5 to 9).
  • Altered Rb expression was found in 21 of 40 patients (52.5%)
  • SV40-positive patients (n = 20, 18 died) had a median survival of 25.00 months (95% CI 10.21 to 39.79); log-rank 10.88, P = 0.001
  • SV40-negative patients (n = 20, 6 died) had a median survival of 47.08 months (95% CI 42.89 to 51.27)
  • Patients with a positive asbestos history (n = 31, 23 died) had a median survival of 32.08 months (95% CI 21.85 to 42.32); log-rank 9.49, P = 0.002
  • Patients with a negative asbestos history (n = 9, 1 died) had a median survival of 47.08 months (95% CI printed as 47.08 to 47.08)
  • Patients positive for both SV40 and asbestos history (n = 18) all died during follow-up, with a median survival of 21.75 months
  • The multivariate analysis was a Cox model considering SV40, asbestos history and their combination. Only combined positivity was an independent factor affecting overall survival (P = 0.001).
  • For combined positivity, the Discussion reports 5.7 (95% CI 2.1 to 15.5; P = 0.001) and calls it 'odds of death'. This is inconsistent with the methods, which say the Cox model was used to estimate hazard ratios.
  • On univariate analysis, tumor stage (P = 0.03) and performance status II (P = 0.04) were also significantly associated with overall survival
  • Follow-up ranged from 6 to 48 months (median 28.8 months)
• The authors' conclusion: The authors concluded that both SV40 infection and asbestos exposure contribute to the development and progression of mesothelioma in Egyptian patients. They also concluded that combined positivity is detrimental to clinical outcome, though the exact mechanisms remain to be clarified.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, SV40, Immunohistochemistry, Asbestos Exposure, Overall Survival, Performance Status, Multivariate Analysis, Synergistic Effect.

Related studies

• Simian virus 40 transformation, malignant mesothelioma and brain tumors — F. Qi, M. Carbone, et al. (2011)
• Simian virus 40 sequences in blood specimens from healthy individuals of Casale Monferrato, an industrial town with a history of asbestos pollution — C. Pancaldi, V. Balatti, et al. (2009)
• Mesothelioma mortality in Europe: impact of asbestos consumption and simian virus 40 — K. Leithner, A. Leithner, et al. (2006)
• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)
• No association between simian virus 40 and diffuse malignant mesothelioma of the pleura in Iranian patients: a molecular and epidemiologic case-control study of 60 patients — Z. Mohammad-Taheri, S.A. Nadji, et al. (2013)
• Evidence against a role for SV40 infection in human mesotheliomas and high risk of false-positive PCR results owing to presence of SV40 sequences in common laboratory plasmids — F. López-Ríos, P.B. Illei, et al. (2004)

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