Telomerase activity analyzed with TRAP in situ provides additional information in effusions remaining equivocal after immunocytochemistry and hyaluronan analysis

Our plain-English summary of Telomerase activity analyzed with TRAP in situ provides additional information in effusions remaining equivocal after immunocytochemistry and hyaluronan analysis, by E. Adell, A. Dejmek (Diagnostic Cytopathology, 2014).

The study

• Authors: E. Adell, A. Dejmek
• Journal: Diagnostic Cytopathology
• Published: 2014;42(12):1051-7
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Cytology is central in the diagnosis of malignancy in effusions. Ancillary techniques, mainly immunocytochemistry, have considerably improved the sensitivity but some 10% of all cases remain equivocal and require the addition of new diagnostic modalities. We have previously shown that strong nuclear telomerase activity determined with Telomere Repeat Amplification Protocol (TRAP) in situ is specific for malignant cells and could be a candidate for an additional test. Thirty effusions remaining diagnostically equivocal after the use of immunocytochemistry and the determination of the hyaluronan content were reviewed and their TRAP in situ reactivity was related to the definitive diagnoses based on all available data. There were seven effusions from patients with definitive benign diagnoses and 23 effusions from patients with definitive malignant diagnoses. Strong telomerase activity was seen only in effusions from patients with definitive malignant diagnosis, all effusions from patients with benign disease lacking strong telomerase activity, whereas eight of the malignant cases, including three cases of epithelial mesothelioma, showed strong reactivity. Strong nuclear TRAP in situ reactivity was demonstrated only in effusions from patients with verified malignant disease. Although the study is small, it suggests that TRAP in situ activity provides diagnostic information in about one-third of effusions remaining cytologically equivocal after the use of current ancillary techniques. The most striking diagnostic improvement appears to be gained in epithelial mesotheliomas.

© 2014 Wiley Periodicals, Inc.

In plain English

This Swedish study tested whether TRAP in situ, a lab test for telomerase (an enzyme active in many cancer cells), could help with fluid samples (effusions) from the pleura and peritoneum. The samples had stayed unclear after standard work-up, using immunocytochemistry where possible and hyaluronan testing when mesothelioma was a possible diagnosis. The authors retrospectively selected 30 such effusions tested in Malmö from 2003 to 2010 and compared results with definitive diagnoses as of 2013: 7 benign, 23 malignant. Strong nuclear telomerase activity was found in 8 of the 23 malignant cases and in none of the 7 benign cases. A one-tailed Fisher exact test of this gave a p-value of 0.08, which the authors linked to the small number of benign cases. All three cases of epithelial malignant mesothelioma showed strong activity. Results varied in the mesenchymal malignant mesotheliomas and other cancers. The authors concluded that, although the material was small, strong reactivity indicated malignant cells, adding information in about one-third of these unclear effusions from patients with malignant disease. The study did not examine asbestos exposure.

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: Retrospective diagnostic study comparing telomerase test results (TRAP in situ) on diagnostically unclear effusions with patients' later definitive diagnoses
• Who was studied: 30 pleural and peritoneal effusions with non-conclusive cytology, from the Department of Clinical Cytology and Pathology, Skåne University Hospital, Malmö, Sweden, tested 2003 to 2010. 7 were from patients with a definitive benign diagnosis and 23 from patients with a definitive malignant diagnosis, including 8 malignant mesotheliomas (5 mesenchymal, 3 epithelial). Cytology had included immunocytochemistry when applicable (not possible in four cases) and hyaluronan measurement when mesothelioma was a differential diagnosis.
• Exposure: Not applicable. The study evaluated a diagnostic test (telomerase activity measured by TRAP in situ) and did not report asbestos or other exposures.
• Main results:
  • Strong nuclear telomerase reactivity was found in 8 of 23 effusions from patients with a definitive malignant diagnosis.
  • None of the 7 benign cases showed strong reactivity. Two benign cases showed weak reactivity and one showed moderate reactivity; that case's definitive diagnosis, amyloidosis, was based on autopsy.
  • Among the malignant cases, four showed weak and four showed moderate reactivity.
  • Statistical testing of strong telomerase activity as a malignancy marker in these effusions gave P = 0.08 (one-tailed Fisher exact test). The authors attributed this to the small number of benign cases.
  • All three cases of epithelial malignant mesothelioma showed strong reactivity, unlike the other malignancies, in which activity varied (P = 0.03, Fisher's exact test). In the mesenchymal malignant mesotheliomas, reactivity varied: in the case table, four were negative and one was moderate.
  • The TRAP in situ test failed technically in 3% of cases in the authors' laboratory.
• The authors' conclusion: The authors concluded that, although the material was small, strong nuclear TRAP reactivity indicated malignant cells in effusions that remained equivocal after established ancillary techniques. They said it provided additional information in about one-third of those effusions from patients with malignant disease, with the most striking improvement appearing in epithelial mesothelioma.
• Limitations the authors state:
  • The number of cases was small, especially the number of benign cases.
  • The numbers of cases of different malignancies were too small for subgroup analysis.
  • Weak and moderate reactivity could come from non-malignant cells, such as lymphocytes or proliferative mesothelial cells.
  • Some samples may not have contained malignant cells, and some tumor cells may not express telomerase. The authors noted that mesenchymal mesotheliomas seldom shed tumor cells into the fluid.
  • Whether an effusion itself was malignant cannot be confirmed, even in a patient with known cancer, without a concurrent biopsy from the serosal cavity, which was seldom done.

Topics

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

Medical terms in this study, explained in our Lexicon: Cytology, Mesothelioma.

Related studies

• Telomerase activity in human pleural mesothelioma — K. Dhaene, R. Hübner, et al. (1998)
• SV40 infection induces telomerase activity in human mesothelial cells — R. Foddis, A. De Rienzo, et al. (2002)
• Telomerase activity in pleural malignant mesotheliomas — A.Y. Au, T. Hackl, et al. (2011)
• Telomeres and telomerase in mesothelioma: Pathophysiology, biomarkers and emerging therapeutic strategies (Review) — D. Andreikos, D.A. Spandidos, et al. (2025)
• Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine — S. Thunold, E. Hernes, et al. (2025)
• Cytological differential diagnosis among adenocarcinoma, epithelial mesothelioma, and reactive mesothelial cells in serous effusions by immunocytochemistry — X.Y. Su, G.D. Li, et al. (2011)

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