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

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.