Analysis of TERT mRNA Levels and Clinicopathological Features in Patients with Peritoneal Mesothelioma

Our plain-English summary of Analysis of TERT mRNA Levels and Clinicopathological Features in Patients with Peritoneal Mesothelioma, by A. d'Amati, G. Serio, A. Quaranta, et al (Cancers, 2025).

The study

• Authors: A. d'Amati, G. Serio, A. Quaranta, L. Vimercati, M. De Giorgis, L. Lorusso, M. Errede, V. Longo, A. Marzullo, D. Ribatti, T. Annese
• Journal: Cancers
• Published: 2025;17(2)
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background/objectives: Telomerase reverse transcriptase (TERT) is the catalytic subunit of the telomerase enzyme responsible for telomere length maintenance and is an important cancer hallmark. Our study aimed to clarify the mRNA expression of TERT in peritoneal mesothelioma (PeM), and to explore the relationship between its expression and the clinicopathological parameters and prognosis of patients with PeM.

Methods: In a cohort of 13 MpeM patients, we evaluated histotype, nuclear grade, mitotic count, necrosis, inflammation, Ki67, BAP1, MTAP and p16 expression by immunohistochemistry, p16/CDKN2A status by FISH and TERT mRNA expression by RNAscope.

Results: Our results showed several statistical correlations between TERT mRNA-score and other investigated features: (i) a poor positive correlation with BAP1 score (r = 0.06340; p ≤ 0.0001); (ii) a moderate positive correlation with p16 FISH del homo (r = 0.6340; p ≤ 0.0001); (iii) a fair negative correlation with p16 FISH del hetero (r = -0.3965; p ≤ 0.0001); a negative poor correlation with MTAP (r = -0.2443; p ≤ 0.0001); and (iv) a negative fair correlation with inflammatory infiltrate (r = -0.5407; p = 0.0233). Moreover, patients survive for a significantly longer time if they have a low mitotic index adjusted (2-4 mitotic figures per 2 mm2) (p ≤ 0.0001), are male (p = 0.0152), lose BAP1 (p = 0.0152), are p16 positive and present no deletion or heterozygous for p16 (p ≤ 0.01).

Conclusions: TERT is highly expressed in PeM, but it is not one of the crucial factors in evaluating the prognosis of patients. Nevertheless, the results validate the prognostic significance of the mitotic index, BAP1 loss and p16/CDKN2A status.

In plain English

This single-center retrospective study from Bari, Italy, examined archived tumor samples from 13 patients with peritoneal mesothelioma (11 men, 2 women) collected between 2003 and 2017. Seven tumors were epithelioid, six were biphasic, and none were sarcomatoid. The authors measured TERT mRNA, a cancer-related gene product, with a staining method called RNAscope, and compared it and other tissue markers with survival. Asbestos exposure was recorded by questionnaire as occupational or environmental. No fiber types were named. The difference in survival by TERT level was not statistically significant, and no correlation was found between TERT and exposure type or years of exposure. TERT correlated negatively with inflammatory cells in the tumor (r = −0.5407; p = 0.0233). In single-factor comparisons, longer survival was seen with a low mitotic count (p at or below 0.0001), in men (p = 0.0152), with BAP1 loss (p = 0.0152) and with p16 positivity (p = 0.0022). Survival differences between epithelioid and biphasic tumors were not significant (p = 0.0526). The authors concluded that TERT is highly expressed but is not one of the crucial factors in prognosis. They noted the small cohort, the missing sarcomatoid cases and the retrospective design.

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: single-center retrospective study of archival tumor tissue (immunohistochemistry, FISH, RNAscope; Kaplan–Meier survival with univariate log-rank tests)
• Who was studied: 13 patients with peritoneal mesothelioma (11 male, 2 female; mean age 66.5 ± 8.6 years), archival tissue collected 2003–2017, University of Bari, Italy; 7 epithelioid and 6 biphasic tumors
• Exposure: Main variable studied was TERT mRNA expression in tumor tissue. Asbestos exposure was recorded by questionnaire and coded as professional (occupational), environmental, or no data. No fiber types are given.
• Main results:
  • The authors report that all 13 cases showed TERT overexpression.
  • No statistically significant difference in survival was found in relation to TERT mRNA expression.
  • TERT mRNA showed no correlation with type of exposure or years of exposure.
  • TERT mRNA score had a negative fair correlation with inflammatory infiltrate (r = −0.5407; p = 0.0233).
  • TERT mRNA score had a poor positive correlation with BAP1 score (r = 0.06340; p ≤0.0001), as printed.
  • TERT mRNA score had a moderate positive correlation with p16 FISH homozygous deletion (r = 0.6340; p ≤0.0001).
  • TERT mRNA score had a fair negative correlation with p16 FISH heterozygous deletion (r = −0.3965; p ≤0.0001).
  • Lower adjusted mitotic index (2–4 mitoses per 2 mm2) was associated with longer survival: mean 33.20 months in 5 cases, versus 16.67 months (5–9, 3 cases) and 11.80 months (>10, 5 cases); p ≤0.0001.
  • Men survived longer than women: mean 24.73 months in 11 men versus 1.50 months in 2 women; p = 0.0152.
  • BAP1 loss was associated with longer survival: mean 24.73 months in 11 BAP1-negative cases versus 1.50 months in 2 BAP1-positive cases; p = 0.0152.
  • p16 positivity by immunohistochemistry was associated with longer survival: mean 35.57 months in 7 positive cases versus 4.33 months in 6 negative cases; p = 0.0022.
  • Mean survival was 30.86 months in 7 epithelioid cases and 9.83 months in 6 biphasic cases. The difference was not statistically significant (p = 0.0526).
• The authors' conclusion: The authors concluded that TERT is highly expressed in peritoneal mesothelioma but is not one of the crucial factors for prognosis. They also concluded that the results validate the prognostic significance of the mitotic index, BAP1 loss and p16/CDKN2A status.
• Limitations the authors state:
  • Small cohort size
  • No sarcomatoid cases were included
  • Retrospective design limits the strength of the conclusions
  • The better survival in men may reflect the small cohort and earlier follow-up of men with known occupational asbestos exposure

Topics

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Prognosis, Nuclear Grade, Mitotic Count, Necrosis, Inflammation, BAP1, MTAP.

Related studies

• MicroRNA and mRNA features of malignant pleural mesothelioma and benign asbestos-related pleural effusion — G. Ak, S.C. Tomaszek, et al. (2015)
• Changes in DNA 8-hydroxyguanine levels, 8-hydroxyguanine repair activity, and hOGG1 and hMTH1 mRNA expression in human lung alveolar epithelial cells induced by crocidolite asbestos — H.N. Kim, Y. Morimoto, et al. (2001)
• Soluble mesothelin related peptides (SMRP) and osteopontin as protein biomarkers for malignant mesothelioma: analytical validation of ELISA based assays and characterization at mRNA and protein levels — A.J. Rai, R.M. Flores, et al. (2010)
• The genetic susceptibility in the development of malignant pleural mesothelioma: somatic and germline variants, clinicopathological features and implication in practical medical/surgical care: a narrative review — M.T. Congedo, E.C. West, et al. (2024)
• Clinicopathological features of radiological early malignant pleural mesothelioma with no apparent tumor or pleural thickening — A. Nakamura, M. Hashimoto, et al. (2021)
• Serum Levels of N- and C-ERC/Mesothelin and Clinicopathological Factors in Mesothelioma Patients and Those without Mesothelioma — A.I. Koyanagi, K. Kajino, et al. (2023)

Browse more research in Cancers, or return to medical research.