IBCN 2017: Molecular Subtyping II

Lisbon, Portugal (UroToday.com) Deb Sundi from Ohio State, Columbus, OH presented his abstract ‘Predictive impact of intrinsic bladder cancer subtypes on survival after radical cystectomy’. In 257 patients were nearly evenly distributed among the 3 intrinsic subtypes, and 146 (54%) underwent NAC. Consistent with our prior findings, p53-like tumors demonstrated the lowest downstaging rates after NAC (31%), as compared to 51% for basal and 55% for luminal (p=0.055). Among patients who did not receive NAC, OS was similar among subtypes. Among patients who underwent NAC, OS was significantly longer among patients with basal tumors (p=0.0214). Reciprocally, OS was longer for patients who underwent NAC (as compared to upfront RC) among patients with basal tumors, but not among patients with luminal or p53-like subtypes. These findings suggest that a basal gene signature in bladder cancer is associated with benefit after NAC, and that the p53-like gene signature appears to confer chemo-resistance as assessed by pathologic downstaging. Further research and clinical trials are needed to validate these data.

Roland Seiler from University of British Columbia, Vancouver, British Columbia presented his abstract ‘Plasticity in muscle-invasive bladder cancer before and after cisplatin-based neoadjuvant chemotherapy’. Radical cystectomy (RC) samples were available for gene expression analysis from 134 patients treated with cisplatin-based NAC who had residual MIBC, of which 116 had matched pre-NAC samples. Consensus clusters (CC) 1 and 2 expressed genes consistent with a basal-like (KRT5/6, KRT14) and a luminallike (GATA3, PPARG) phenotype, respectively. CC3 expressed a strong T-cell signature, markers for T-cell receptor and chemokine signaling as well as checkpoint molecules (CTLA4, CD80). Conversely, CC4 was associated with wound healing/scarring (MYH11, SHH, CNN1). This ‘scar-like’ character of CC4 was highly consistent with the scar samples (n=21). IHC for GATA3, PPARG, CD44 and CD8 confirmed the biological characteristics of CC1-4. Pair-wise comparison of samples before and after NAC revealed that pre-NAC samples with basal characteristics were represented in all four post-NAC clusters, but luminal pre-NAC tumors were almost exclusively CC2-4 after NAC. Despite being pathological non-responders, patients in CC4 had favorable prognosis compared to patients in CC1-3 (p=0.027). In post-NAC MIBC four biologically and clinically distinct clusters (CC1 basal, CC2 luminal, CC3 infiltrated, CC4 scar-like) were identified. Further validation of these results are needed prior to clinical application.

Antonia Vlahou from Academy of Athens, Athens, Greece presented her abstract ‘Proteomics phenotyping of bladder cancer’. Tissue specimens from patients with non-muscle invasive (NMIBC) and muscle invasive bladder cancer (MIBC) were analyzed by high resolution liquid chromatography coupled to tandem mass spectrometry. They noted multiple expected protein changes associated with the invasive phenotype (such as in annexins, alpha actinins, TGFBI, cadherins, or cathepsins) as well as additional novel findings, such as changes in BRO1 domain-containing protein BROX, alpha-L-fucosidase and others further confirmed by immunohistochemistry. In silico analysis predicted, among others, a significant activation of protein synthesis. Proteomics characterization of BC to support molecular integrative studies are needed and these findings complement genotype and molecular subtyping data.

Speaker(s): Deb Sundi, Ohio State, Columbus, OH; Roland Seiler, University of British Columbia, Vancouver, BC; Antonia Vlahou, Academy of Athens, Athens, Greece

Written by: Stephen B. Williams, M.D., Associate Professor, Division of Urology, The University of Texas Medical Branch, Galveston, TX. and Ashish M. Kamat, M.D. Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX., at the International Bladder Cancer Network - October 21, 2017- Lisbon, Portugal

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