Mutations in STAG2 cause complete loss of STAG2 protein in approximately one-third of non-muscle-invasive bladder cancers (NMIBCs). STAG2 protein expression is easily determined via immunohistochemistry (IHC) and published data suggest that loss of STAG2 expression is a good prognostic indicator in NMIBC.
To confirm the relationship between STAG2 protein expression and clinical outcomes and tumour characteristics in NMIBC.
IHC was used to determine STAG2 expression in 748 incident urothelial bladder cancers (UBCs) and recurrence-free, progression-free, and disease-specific survival were compared for patients with and without STAG2 loss. Exome and RNA sequencing were used to explore links between STAG2 loss and tumour molecular characteristics.
STAG2 loss was observed in 19% of UBC patients and was 1.6-fold more common among female patients. Loss was frequent among grade 1 pTa tumours (40%), decreasing with stage and grade to only 5% among grade 3 pT2+ tumours. Loss was associated with fewer copy-number changes and less aggressive expression subtypes. In UBC, STAG2 loss was a highly significant prognostic indicator of better disease-free survival but was not independent of stage and grade. STAG2 loss was not a statistically significant predictor of NMIBC recurrence. STAG2 loss was significantly associated with better progression-free survival in NMIBC and appeared to be more prognostic for males than for females.
A simple IHC-based STAG2 test shows promise for identifying NMIBC patients at lower risk of progression to MIBC for whom more conservative treatments may be suitable.
A protein called STAG2 is frequently lost in early bladder cancers, most often in less aggressive tumours. STAG2 loss is easily measured and could be used as a biomarker to help guide treatment decisions.
European urology open science. 2022 Mar 04*** epublish ***
Naheema S Gordon, Nada Humayun-Zakaria, Anshita Goel, Ben Abbotts, Maurice P Zeegers, K K Cheng, Nicholas D James, Roland Arnold, Richard T Bryan, Douglas G Ward
Bladder Cancer Research Centre, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Care and Public Health Research Institute, School of Nutrition and Translational Research in Metabolism, Department of Epidemiology, Maastricht University, Maastricht, The Netherlands., Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Institute of Cancer Research, London, UK.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/35495284