STAG2 Is a Biomarker for Prediction of Recurrence and Progression in Papillary Non–Muscle-Invasive Bladder Cancer
2018
Purpose: Most bladder cancers are early-stage tumors known as papillary non–muscle-invasive bladder cancer (NMIBC). After resection, up to 70% of NMIBCs recur locally, and up to 20% of these recurrences progress to muscle invasion. There is an unmet need for additional biomarkers for stratifying tumors based on their risk of recurrence and progression. We previously identified STAG2 as among the most commonly mutated genes in NMIBC and provided initial evidence in a pilot
cohortthat STAG2 -mutant tumors recurred less frequently than STAG2 wild-type tumors. Here, we report a STAG2 biomarker validation study using two independent
cohortsof clinically annotated papillary NMIBC tumors from the
United Statesand
Europe. Experimental Design: The value of STAG2
immunostainingfor prediction of recurrence was initially evaluated in a
cohortof 82 patients with papillary NMIBC (“Georgetown
cohort”). Next, the value of STAG2
immunostainingfor prediction of progression to muscle invasion was evaluated in a progressor-enriched
cohortof 253 patients with papillary NMIBC (“Aarhus
cohort”). Results: In the Georgetown
cohort, 52% of NMIBC tumors with intact STAG2 expression recurred, whereas 25% of STAG2-deficient tumors recurred ( P = 0.02). Multivariable analysis identified intact STAG2 expression as an independent predictor of recurrence (HR = 2.4; P = 0.05). In the progressor-enriched Aarhus
cohort, 38% of tumors with intact STAG2 expression progressed within 5 years, versus 16% of STAG2-deficient tumors ( P P = 0.05). Conclusions: STAG2 IHC is a simple, binary, new assay for risk stratification in papillary NMIBC. Clin Cancer Res; 1–9. ©2018 AACR.
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