MP88-20 EVALUATION OF THE BIOLOGICAL BASIS OF UROTHELIAL CARCINOMA WITH SQUAMOUS DIFFERENTIATION

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology V1 Apr 2016MP88-20 EVALUATION OF THE BIOLOGICAL BASIS OF UROTHELIAL CARCINOMA WITH SQUAMOUS DIFFERENTIATION Thomas Sanford, Maxwell Meng, and Sima Porten Thomas SanfordThomas Sanford More articles by this author , Maxwell MengMaxwell Meng More articles by this author , and Sima PortenSima Porten More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2438AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Squamous differentiation is found in up to 60% of patients with urothelial carcinoma of the bladder. There is conflicting evidence regarding clinical relevance of aberrant urothelial differentiation - both population-based and retrospective studies have reported conflicting results regarding the correlation between squamous differentiation and poor prognosis/advanced stage. The biology of these tumors is poorly understood but some suggest that urothelial carcinoma with extensive squamous differentiation may resemble pure squamous tumors with similar responses to chemotherapy, radiation, and higher rates of local recurrence. Our aim was to compare urothelial carcinoma with squamous differentiation with urothelial carcinoma without any variant histology at the genomic level to better elucidate targetable differences. METHODS We reviewed pathology reports for 412 patients with urothelial carcinoma from The Cancer Genome Atlas Project (TCGA) to identify patients with any amount squamous differentiation. Copy number alteration data obtained via the GISTC algorithm was downloaded from cbioportal.com. Chi square analysis was used to compare chromosomal amplifications in samples with squamous differentiation compared with samples that had no amount of variant histology. RESULTS 50 patients (12%) had a report of at least 1% squamous differentiation. Of these 50 patients with evidence of squamous differentiation, there were 15 patients in which there was a comment regarding the percent of involvement. On average, 17% of the sample had squamous differentiation. A total of 257 (62%) of patients had no variant histology. Our analysis showed there were multiple specific sites in the 3q21-26 chromosomal region that were amplified in samples with squamous histology compared with pure urothelial carcinoma histology. The specific sites found to be amplified included SOX2 and PIK3. CONCLUSIONS Amplifications of chromosome 3q21-26 were enriched in patients with squamous differentiation compared to those with pure urothelial carcinoma of the bladder. Amplification of this region has been reported in squamous transformation in multiple sites, including lung cancer. This study shows that, similar to other cancers, SOX2 may be necessary for squamous transformation. Furthermore, squamous cancer, which has traditionally been chemo-resistant, may respond to agents that target amplifications of genes known to be found on the long arm of chromosome 3 including the PIK3-Akt pathway. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1136 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Thomas Sanford More articles by this author Maxwell Meng More articles by this author Sima Porten More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...