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Updated: Jun 10, 2025
Magnetic Resonance Imaging Assessment of Carcinogen-induced Murine Bladder Tumors
Published on: March 29, 2019
Integrating Genetic Alterations and Histopathological Features for Enhanced Risk Stratification in
Melinda Lillesand1,2, Vebjørn Kvikstad3, Einar Gudlaugsson1
1Department of Pathology, Stavanger University Hospital, 4011 Stavanger, Norway.
Background:
Urothelial carcinoma presents as non-muscle-invasive bladder cancer (NMIBC) in ~75% of primary cases. Addressing the limitations of the TNM and WHO04/16 classification systems, this study investigates genetic alterations, the mitotic activity index (MAI), and immunohistochemistry (IHC) markers CK20, p53, and CD25 as better prognostic biomarkers in NMIBC.
Methods:
Using the Oncomine™ Focus Assay for targeted next-generation sequencing (NGS), 409 single-nucleotide variations (SNVs) and 193 copy number variations (CNVs) were identified across 287 patients with TaT1 tumors.
Results:
FGFR3 and PIK3CA alterations were significantly more prevalent in Ta tumors, while T1 tumors had significant ERBB2 alterations. Low-grade (LG) tumors were enriched with FGFR3 alterations, while high-grade (HG) tumors were significantly associated with ERBB2 alterations, as well as FGFR1 and CCND1 amplifications. FGFR3 alterations were linked to shorter recurrence-free survival (RFS; p = 0.033) but improved progression-free survival (PFS; p < 0.001). Conversely, ERBB2 alterations (p < 0.001), ERBB3 mutations (p = 0.044), and both MYC (p < 0.001) and MYCN (p = 0.011) amplifications were associated with shorter PFS. Survival analysis of gene sets revealed inverse associations between PIK3CA and ERBB2 (p = 0.003), as well as PIK3CA and MYC (p = 0.005), with PFS.
Conclusions:
In multivariate Cox regression, MAI was the strongest predictor for PFS. Integrating genetic alterations and histopathological features may improve risk stratification in NMIBC.
