Pd15-03 an Intervention to Improve Bladder Cancer Knowledge and Treatment Decision Making in Patients With Muscle Invasive Bladder Cancer: a Pilot Study
Year: 2018
Type: article
Study design: Observational Study
Abstract: INTRODUCTION AND OBJECTIVES: Muscle invasive bladder cancer (MIBC) is a highly aggressive disease, often presenting with heterogeneous clinical and pathological features.Though these tumors are commonly urothelial, secondary variant histology is frequently encountered.Recent transcriptome profiling studies have revealed MIBC can be divided into at least four distinct molecular subtypes, with the benefits of neoadjuvant chemotherapy (NAC) potentially varying between subtypes.The presence of secondary variant histology may alter this molecular profile and the treatment responses of these tumors.In this study, we report the genomic characterization of a large prospective MIBC cohort enriched with secondary variant histology.METHODS: The cohort consisted of 173 patients diagnosed with urothelial MIBC who received the Decipher Bladder genomic subtyping classifier test (GenomeDx Biosciences Laboratory, San Diego, CA).Descriptions of secondary variant histology were abstracted from clinical pathology reports of submitted cases.TURBT tissue samples were profiled using a high-density genome-wide expression microarray and de-identified for GRID software analysis in R-studio (v3.3.1).RESULTS: The cohort included 136 males and 32 females with a mean age of 72Æ9 at TURBT.A total of 49 cases (28%) had variant histology including non-urothelial (squamous [24], neuroendocrine [4], glandular [4]) and urothelial (micropapillary [6], sarcomatoid [5], plasmacytoid [2], nested [3], clear cell [1]) variants.Molecular subtyping revealed 77% of variant cases were either pure basal-like (22) or basal claudin-low ( 16), with fewer cases being luminal (7) or infiltrated luminal (4).Squamous cases had profiles consistent with basal tumors, while neuroendocrine cases had high MKI67 and neuronal marker expression.Micropapillary profiles had high CDH3 and MUC1 expression levels.Sarcomatoid tumors were driven by robust expression of EMT markers, including VIM, ZEB1 and ZEB2, with a corresponding loss of CDH1 expression.One plasmacytoid case expressed high levels of CDH1 RNA, but was negative for IHC, while the other case had low CDH1 RNA and lacked IHC data.CONCLUSIONS: Secondary variant histology in MIBC contributes to the molecular heterogeneity of these tumors, with the majority of variant histology cases in this cohort being associated with basal MIBC subtypes.These findings may have implications for tailoring NAC by molecular subtype and may contribute to the varied clinical responses encountered in treating patients with variant histology.
Source: The Journal of Urology
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2795640285