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Telomerase reverse transcriptase mutation and the p53 pathway in T1 urinary bladder cancer
Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0001-9867-8706
Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
2022 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 129, no 5, p. 601-609Article in journal (Refereed) Published
Abstract [en]

Objective To study the telomerase reverse transcriptase (TERT) mutation and the p53 pathway in T1 urinary bladder cancer (UBC). Materials and Methods 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, inclusive. Given that p53 and TERT are important factors for tumour proliferation, although their interrelationships are unknown, we assessed both the TERT and the p53 mutations. Furthermore, we conducted a p53 immunohistochemistry (IHC) analysis using two thresholds for p53 positivity: 10% of tumour cells and 50% of tumour cells (p53 IHC50%). Cox proportional hazards analysis and Kaplan-Meier curves were used to study time to tumour progression. Results Out of 158 patients, we observed the TERT mutation in 74 (47%), the p53 mutation in 48 (30%), and p53 IHC50% positivity in 72 patients (46%). The TERT mutation was more common in p53 mutation-positive patients (P = 0.009), and the latter group also had more patients with p53 IHC50%-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 TERT mutation positivity and p53 mutation positivity, a longer time to progression was observed in the group with p53 IHC50% positivity compared to the group with p53 IHC50%-negative tumours. Conclusions 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.

Place, publisher, year, edition, pages
WILEY , 2022. Vol. 129, no 5, p. 601-609
Keywords [en]
TERT mutation; p53 pathway; urinary bladder cancer; p53 immunohistochemistry; p53 mutation; #BladderCancer; #blcsm
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-180024DOI: 10.1111/bju.15490ISI: 000669406500001PubMedID: 34028171Scopus ID: 2-s2.0-85109075817OAI: oai:DiVA.org:liu-180024DiVA, id: diva2:1601502
Available from: 2021-10-08 Created: 2021-10-08 Last updated: 2023-05-04

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Jahnson, StaffanSöderkvist, PeterAbdul-Sattar Aljabery, FirasOlsson, Hans
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Urology in ÖstergötlandDivision of Cell BiologyDivision of NeurobiologyClinical pathology
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