Retrospective analysis of an alternative immuno-score in clinical management of patients with pT2 urothelial carcinoma.

Abstract

e17038 Background: Within the mapping of the genome through the TCGA collaborative project, the urothelial carcinoma (UC) has recently revealed major intrinsic molecular subtypes, Basal, Luminal and Neural muscle-invasive UC. Here we propose a fast and standardized immuno-phenotypical score classification (Piescore), as a surrogate, which may discriminate Luminal, Basal or Neural UC and may correlate with histological and clinical variables in a mono-institutional cohort of patients treated with trans-urethral resection (TURB) and radical cystectomy (RC). Methods: This is a retrospective study of TURB specimens that harbored foci of HG pT2 (MIBC) UC from 116 pts who underwent RC. All the samples were assessed for immunohistochemical pattern, using relevant gene-expression-based markers for Basal type (CD44, CK5/6) and Luminal type (CK20 and pPARg). Piescore, investigated in both superficial and muscle-invasive component of the tumors, divided Basal and Luminal UC-types when at least 3 of the 4 markers were consistent with a specific phenotype, Mixed if two luminal and two basal markers were present simultaneously, and Neural when all four markers were negative. Results: Overall in muscle-invasive component, Piescore identified Basal phenotypes in 49 pts (42,2%), Luminal in 38 pts (32,7%), and Mixed in 9 pts (7,8%). No expression was identified in 20 pts (17,2%): 7 cases with morphological neuroendocrine differentiation and 13 cases with classical urothelial histology, all consistent with Neural phenotype. In 26,7% of cases (31/116 pts) we observed an immuno-phenotypical switch from superficial to deep component: 16 of 31 (51,6%) switched to Basal, 10 (32,2%) switched to Neural, and 5 cases (16,2%) to Mixed phenotype. No cases switched to Luminal. No cases have lost Basal phenotype from superficial to deep component, with the exception of one (switched to Neural). No statistically significant differences in terms of staging, DFS, and OS were observed in the different phenotypes. The presence of phenotypical switch did not affect angioinvasion, staging, DFS, and OS compared to non-switched cases. Conclusions: Piescore immunophenotyping (CD44, CK5/6, CK20 and pPARg) could be a simple surrogate able to stratify UC-TURB patients between Luminal vs Basal type. To our knowledge, preliminary results using the Piescore identify for the first time a phenotypical switch (to basal, Mixed or Neural) between superficial and deeper side of the same tumor, although this phenomenon did not show any prognostic implication.