Abstract 4809: Validation of molecular subtypes of urothelial carcinoma of bladder in multi-institutional and public cohorts

Abstract

Abstract BACKGROUND: Recently we have proposed a molecular sub-classification of conventional urothelial carcinoma which could be divided into two major categories designated as basal and luminal similar to the ones defined for breast cancer. In addition, luminal cancers contain a group of cases characterized by upregulation of p53 regulatory genes and is referred to as p53-like. The purpose of this project is to verify whether such subtypes can be identified in several large independent cohorts of bladder cancers. DESIGN: Gene expression profiles and molecular subtyping were performed by using previously described analytical algorithms on the following bladder cancer patient cohorts: (1) The Cancer Genome Atlas (TCGA) cohort containing tumor tissues from muscle invasive high grade urothelial carcinomas of 129 patients; (2) the MD Anderson Cancer Center (MDA) cohort of fresh frozen tumor tissues which included 65 superficial papillary carcinomas and 77 invasive carcinomas; (3) the Swedish cohort containing fresh frozen tumor samples of 116 superficial papillary tumors and 192 invasive tumors. RESULTS: The three distinct molecular subtypes defined as luminal, p53-like and basal were identified in all three cohorts. The distribution of molecular subtypes in individual cohorts was as follows: the TCGA cohort contained 50 (39%) luminal, 30 (23%) p53-like and 49 (38%) basal tumors; the MDA cohort contained 54 (38%) luminal, 61 (43%) p53-like and 27 (19%) basal; the Swedish cohort contained 102 (33%) luminal, 129 (42%) p-53 like and 77 (25%) basal tumors. Interestingly, in the MDA and Swedish cohorts virtually all superficial tumors, of either low or high grade, were of luminal type. CONCLUSION: The conventional bladder cancer can be separated into three distinct molecular subtypes with luminal phenotype defining the vast majority of superficial bladder cancers while muscle invasive tumors can be separated into luminal and basal forms. A subset of luminal cancers is characterized by upregulation of p53 regulatory genes. The identification of subtypes may help to stratify the patients for targeted therapies. Citation Format: Vipulkumar Dadhania, Charles G. Guo, Tadeusz Majewski, Li Zhang, Jolanta Bondaruk, Shizhen Zhang, Woonyoung Choi, David McConkey, Colin Dinney, Keith Baggerly, Bogdan A. Czerniak. Validation of molecular subtypes of urothelial carcinoma of bladder in multi-institutional and public cohorts. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4809. doi:10.1158/1538-7445.AM2015-4809