Expression of p21 in SV40 large T antigen positive human pleural mesothelioma: relationship with survival

Our plain-English summary of Expression of p21 in SV40 large T antigen positive human pleural mesothelioma: relationship with survival, by A. Baldi, A.M. Groeger, V. Esposito, et al (Thorax, 2002).

The study

• Authors: A. Baldi, A.M. Groeger, V. Esposito, R. Cassandro, G. Tonini, T. Battista, M.P. Di Marino, B. Vincenzi, M. Santini, A. Angelini, R. Rossiello, F. Baldi, M.G. Paggi
• Journal: Thorax
• Published: 2002;57(4):353-6
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Mesothelioma is the most commonly occurring primary pleural neoplasm. Several studies have documented an increase in the incidence of this malignancy during the last decades. Although the association between asbestos exposure and development of mesothelioma is generally accepted, the exact mechanism of carcinogenesis is unknown. Recently, Simian virus 40 large T antigen (SV40 Tag) expression has been detected in pleural mesothelioma. The ability of SV40 oncoproteins to inactivate p53 and retinoblastoma tumour suppressor proteins has been proposed as an important step in the pathogenesis of human mesothelioma.

Methods: To obtain a better understanding of the molecular mechanisms of the pathogenesis of mesothelioma, the expression of the cell cycle inhibitor p21(WAF1/CIP1) (p21), a downstream target of p53, was evaluated immunohistochemically in a group of 29 mesothelioma specimens already characterised for the presence of SV40 Tag sequences.

Results: Statistical analysis did not reveal any correlation between p21 expression and histopathological type of mesothelioma using the kappa(2) test (p=0.577). A significant positive relationship was found between p21 expression level and the patients' overall survival according to the Kaplan-Meier survival curves and using a log rank test (median difference in survival 7 months, 95% CI 4.8 to 9.9; p<0.001).

Conclusions: Determination of p21 expression bears a prognostic significance in patients affected with mesothelioma, further underlining the role of SV40 in the pathogenesis of malignant pleural mesothelioma.

In plain English

This laboratory study examined tumour tissue from 29 patients with malignant mesothelioma (16 epithelial, six sarcomatoid and seven mixed). The patients were diagnosed and treated at the Second University of Naples, Italy, between 1980 and 1993. An earlier study had already found Simian virus 40 (SV40) sequences in all 29 tumours. Patient records showed clear asbestos exposure in only three cases. The authors stained the tissue for p21, a protein that slows cell division. They split the tumours into those with less than 10% and more than 10% of cells staining for p21: 15 had less than 10% and 14 had more. Median survival was 5 months in the lower-p21 group and 12 months in the higher-p21 group (median difference 7.0 months, 95% CI 4.8 to 9.9; p less than 0.001). No statistically significant relationship was found between p21 level and tumour type (p=0.577). The authors concluded that p21 expression has prognostic significance in mesothelioma. They said larger studies are needed to confirm this, and noted that a role for SV40 in mesothelioma is not universally accepted.

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: Laboratory study of archived tumour specimens (immunohistochemical staining for p21) with retrospective survival analysis (Kaplan-Meier curves, log rank test)
• Who was studied: 29 malignant mesothelioma specimens (16 epithelial, six sarcomatoid, seven mixed) from open biopsies or pleurectomies. The patients were diagnosed and treated at the Second University of Naples, Italy, from 1980 to 1993. Two patients who died of other causes were excluded.
• Exposure: This is not an asbestos exposure study. The factor studied was p21 protein level in tumours that had all previously tested positive for SV40 sequences. Clear asbestos exposure was documented in only three patients. No fiber types or doses are given.
• Main results:
  • Of the 29 specimens, 15 had less than 10% of cells positive for p21 and the remaining 14 had more than 10%.
  • Median survival was 5 months in the group with less than 10% p21-positive cells and 12 months in the group with more than 10% (median difference 7.0 months, 95% CI 4.8 to 9.9).
  • The survival difference between the two p21 groups was statistically significant by log rank test (p less than 0.001).
  • No statistically significant correlation was found between p21 expression and histological type of mesothelioma (p=0.577).
• The authors' conclusion: The authors concluded that measuring p21 expression has prognostic significance in patients with mesothelioma, and that this further supports a role for SV40 in malignant pleural mesothelioma.
• Limitations the authors state:
  • The authors stated that further studies with more patients are needed to confirm the observations.
  • The authors noted that the role of SV40 in causing mesothelioma is not universally accepted, and that some epidemiological evidence does not support a link.

Topics

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

Medical terms in this study, explained in our Lexicon: SV40, Pleural Mesothelioma, Mesothelioma, Neoplasm, Asbestos Exposure, Mechanism of Carcinogenesis, Overall Survival.

Related studies

• The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas — A. De Luca, A. Baldi, et al. (1997)
• Simian virus 40 large T antigen (SV40LTAg) primer specific DNA amplification in human pleural mesothelioma tissue — C. Pepper, B. Jasani, et al. (1996)
• Simian virus-40 large-T antigen binds p53 in human mesotheliomas — M. Carbone, P. Rizzo, et al. (1997)
• SV40 large T-antigen and human pleural mesothelioma. Screening by polymerase chain reaction and tyramine-amplified immunohistochemistry — K. Dhaene, A. Verhulst, et al. (1999)
• p53, Cip1, and Gadd153 expression following treatment of A549 cells with natural and man-made vitreous fibers — N.F. Johnson, R.J. Jaramillo (1997)
• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)

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