TERT mutation and the p53 pathway in T1 urinary bladder cancer.

To study the telomeras revers transcriptas (TERT) mutation and the p53 pathway in T1 urinary bladder cancer (UBC).

This prospectively performed population-based study included all patients in the Southeast Healthcare Region in Sweden with T1 UBC registered in the period 1992-2001, inclusively. As p53 and TERT are important factors for tumour proliferation although their interrelations are not known we here studied the TERT mutation and the p53 mutation, and a p53 immuno-histochemical examination (IHC) was conducted using p53-positivity both in 10% and in 50% of tumour cells as cut-off levels. Cox Proportional Hazards Analysis and Kaplan-Meier curves were used to study the time to tumour progression.

Out of 158 patients, we observed the TERT mutation in 74 (47%) patients, the p53 mutation in 48 (30%) patients, and p53 IHC 50% positive in 72 (46%) patients. The TERT mutation was more common in p53 mutation-positive patients (p=0.009), and the latter group also had more patients with p53 IHC 50% positive tumour cells (p=0.02). In the TERT mutation-negative tumours a p53-positive-mutation was associated with a shorter time to progression (p=0.03) compared to patients with p53-negative mutation. In contrast, in tumours with both the TERT mutation positive and the p53 mutation positive, a longer time to progression was observed in the group with p53 IHC 50% positive compared to p53 IHC50% negative tumours.

In stage T1 UBC, the combination of the TERT mutation and the p53 mutation was associated with tumour progression. A protective effect of the TERT promotor mutation against tumour progression induced by the p53 mutation and subsequent p53 accumulation in tumour cells might be possible but further investigations are necessary.

BJU international. 2021 May 24 [Epub ahead of print]

Staffan Jahnson, Peter Söderkvist, Firas Aljabery, Hans Olsson

Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, SE 581 85, Linköping, Sweden., Division of Cell Biology and Department of Biomedical and Clinical Biosciences, Linköping University, SE 581 85, Linköping, Sweden., Department of Pathology and Department of Clinical and Experimental Medicine, Medical Faculty, Linköping University, SE 581 85, Linköping, Sweden.