Browsing by Subject "urothelial bladder cancer"

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    The changing reality of urothelial bladder cancer: should non-squamous variant histology be managed as a distinct clinical entity?
    (Wiley, 2015-08) Monn, M. Francesca; Kaimakliotis, Hristos Z.; Cary, K. Clint; Bihrle, Richard; Pedrosa, Jose A.; Masterson, Timothy A.; Foster, Richard S.; Gardner, Thomas A.; Cheng, Liang; Koch, Michael O.; Department of Urology, IU School of Medicine
    Objectives To assess the effect of non-squamous differentiation (non-SQD) variant histology on survival in muscle-invasive bladder urothelial cancer (UC). Patients and Methods A cohort of 411 radical cystectomy (RC) cases performed with curative intent for muscle-invasive primary UC was identified between 2008 and June 2013. Survival analysis was evaluated using Kaplan–Meier methodology comparing non-variant (NV) + SQD histology to non-SQD variant histology (non-SQD variants). Multivariable cox proportional hazards regression assessed all-cause and disease-specific mortality. Results Of the 411 RC cases, 77 (19%) had non-SQD variant histology. The median overall survival (OS) for non-SQD variant histology was 28 months, whereas the NV+SQD group had not reached the median OS at 74 months (log-rank test P < 0.001). After adjusting for sex, age, pathological stage, and any systemic chemotherapy, patients with non-SQD variant histology at RC had a 1.57-times increased adjusted risk of all-cause mortality (P = 0.027) and 1.69-times increased risk of disease-specific mortality (P = 0.030) compared with NV+SQD patients. Conclusions While SQD behaves similarly to NV, non-SQD variant histology portends worse OS and disease-specific survival regardless of neoadjuvant or adjuvant chemotherapy and pathological stage. Non-SQD variants of UC could perhaps be considered a distinct clinical entity in UC with goals for developing new treatment algorithms through novel clinical trials.
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    Micropapillary urothelial carcinoma: evaluation of HER2 status and immunohistochemical characterization of the molecular subtype
    (Elsevier, 2018) Zinnall, Ulrike; Weyerer, Veronika; Compérat, Eva; Camparo, Philippe; Gaisa, Nadine T.; Knuechel-Clarke, Ruth; Perren, Aurel; Lugli, Alessandro; Toma, Marieta; Baretton, Gustavo; Kristiansen, Glen; Wirtz, Ralf M.; Cheng, Liang; Wullich, Bernd; Stoehr, Robert; Hartmann, Arndt; Bertz, Simone; Pathology and Laboratory Medicine, School of Medicine
    Comprehensive molecular analyses of urothelial bladder cancer (UBC) have defined distinct subtypes with potential therapeutic implications. In this study, we focused on micropapillary urothelial carcinoma (MPUC), an aggressive, histomorphologically defined rare variant. Apart from genetic alterations shared with conventional UBC, alterations of the HER2 gene have been reported in higher frequencies. However, only small cohorts of MPUCs have been analyzed, and the real impact is still unclear. We collected a cohort of 94 MPUCs and immunohistochemically tested HER2, basal (CD44, CK5, EGFR, p63) and luminal (CD24, FOXA1, GATA3, CK20) markers to allocate MPUC to a molecular subtype. Additionally, HER2 amplification status was assigned by chromogenic in situ hybridization. Sanger sequencing of exon 4 and 8 was used to test for HER2 mutations. Kruskal-Wallis test was calculated to compare marker distribution between proportions of the MPUC component. HER2 2+/3+ staining scores were identified in 39.6% of 91 analyzed MPUCs and were not differentially distributed among the proportion of the MPUC component (P = .89). Additionally, CISH analysis revealed 30% of HER2-amplified tumors independently of the MPUC fraction. In 6/90 evaluable MPUCs, a p.S310F HER2 mutation was detected. Overexpression of luminal markers was observed in the majority of MPUC. Our investigations of the largest cohort of analyzed MPUC demonstrate that HER2 overexpression and amplifications are common genetic alterations and identification of overexpressed luminal markers allows subclassification to the luminal subtype. These findings highlight the need of histomorphological recognition of MPUC and analysis of HER2 status and the luminal molecular subtype for potential targeted therapeutic strategies.