Absence of SV-40 large T antigen (Tag) in malignant mesothelioma effusions: an immunocytochemical study

Our plain-English summary of Absence of SV-40 large T antigen (Tag) in malignant mesothelioma effusions: an immunocytochemical study, by A. Simsir, P. Fetsch, C.W. Bedrossian, et al (Diagnostic Cytopathology, 2001).

The study

• Authors: A. Simsir, P. Fetsch, C.W. Bedrossian, O.B. Ioffe, A. Abati
• Journal: Diagnostic Cytopathology
• Published: 2001;25(4):203-7
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Simian Virus 40 (SV 40) was recently implicated in the pathogenesis of malignant mesothelioma. The oncogenic capacity of SV-40 is a function of a nuclear protein, the large T antigen (Tag). SV-40 Tag DNA sequences are detected by the polymerase chain reaction in 40-80% of malignant mesothelial proliferations. However, the role of immunohistochemistry (IHC) in demonstrating the nuclear localization of Tag is controversial. We sought to determine the clinical utility of SV-40 Tag IHC in pleural effusion cytology as an ancillary tool in the cytologic diagnosis of malignant mesothelioma (MM). Formalin-fixed, paraffin-embedded cell block sections from 100 pleural effusions (32 MMs, 25 benign reactive, 43 metastatic adenocarcinomas) were immunostained for the SV-40 anti-Tag, using two primary monoclonal SV-40 Tag antibodies: clone Pab 416 and clone Pab 101. Despite strong and consistent immunoreactivity in positive controls, no nuclear immunostaining was observed in any case. We believe the small sample size in cytology cell block sections, the low viral copy number in infected cells, and the effect of formalin fixation may have resulted in absence of immunoreactivity. The role of SV-40 Tag IHC in diagnostic cytopathology remains unclear unless further studies reliably show its detection.

Copyright 2001 Wiley-Liss, Inc.

In plain English

This laboratory study tested whether a protein made by simian virus 40 (SV-40), called the large T antigen (Tag), could be found in fluid that collects around the lungs (pleural effusions), as a possible aid to diagnosing malignant mesothelioma. The authors stained preserved, formalin-fixed cell block sections from 100 pleural effusions: 32 malignant mesotheliomas, 25 benign reactive effusions and 43 metastatic adenocarcinomas. They used two antibodies against SV-40 Tag, clone Pab 416 and clone Pab 101. Control cells transformed by SV-40 showed strong nuclear staining in more than 50% of cells with both antibodies. No staining for Tag was found in any of the mesothelioma, reactive or adenocarcinoma samples. The study did not measure asbestos exposure. The authors suggested that small cell samples, low amounts of virus in infected cells and formalin fixation may explain the negative results. They also said the cases might truly have lacked SV-40. The authors concluded that the role of SV-40 Tag testing in diagnostic cytopathology remains unclear unless further studies reliably show its detection.

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 immunohistochemistry study of archived pleural effusion cytology samples
• Who was studied: Cell block sections from 100 pleural effusions: 32 malignant mesotheliomas, 25 benign reactive effusions and 43 metastatic adenocarcinomas (7 lung, 3 prostate, 10 breast, 11 ovary, 1 fallopian tube, 3 colon, 4 pancreas, 2 stomach, 2 esophagus primaries). Where and when the samples were collected is not stated.
• Exposure: Detection of SV-40 large T antigen using two monoclonal antibodies, clone Pab 416 and clone Pab 101. Asbestos exposure was not studied.
• Main results:
  • Positive control cells (SV-40 transformed human glomerular epithelial cells) showed strong nuclear staining in more than 50% of cells with both antibodies.
  • The negative control was negative in each run.
  • No staining for SV-40 Tag was seen in any of the 32 malignant mesothelioma, 25 reactive or 43 metastatic adenocarcinoma samples.
• The authors' conclusion: The authors concluded that the role of SV-40 Tag in diagnostic cytopathology is unclear unless further studies reliably show its detection by immunohistochemistry and its specificity for malignant mesothelioma.
• Limitations the authors state:
  • The authors suggested that small sample size in cytology cell blocks, low viral copy number in infected cells, and formalin fixation may have caused the negative results.
  • The number of tumor cells in the samples varied from just a few to numerous.
  • The authors said the unstained cases might truly be SV-40 negative. The study did not test them with molecular techniques.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Immunohistochemistry, Pleural Effusion, Cytology, Cell Block, Adenocarcinoma, Monoclonal, Cytopathology.

Related studies

• Simian virus-40 large-T antigen binds p53 in human mesotheliomas — M. Carbone, P. Rizzo, et al. (1997)
• 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)
• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)
• Effect of simian virus large T antigen expression on cell cycle control and apoptosis in rat pleural mesothelial cells exposed to DNA damaging agents — V. Levresse, S. Moritz, et al. (1998)
• Expression of p21 in SV40 large T antigen positive human pleural mesothelioma: relationship with survival — A. Baldi, A.M. Groeger, et al. (2002)
• SV40 large T-antigen and human pleural mesothelioma. Screening by polymerase chain reaction and tyramine-amplified immunohistochemistry — K. Dhaene, A. Verhulst, et al. (1999)

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