MP55-07 PREDICTIVE AND PROGNOSTIC ROLE OF A SIMPLE IMMUNO-PHENOTYPICAL SCORE IN CLINICAL MANAGEMENT OF PATIENTS WITH PT2 INVASIVE UROTHELIAL CARCINOMA

Abstract

INTRODUCTION AND OBJECTIVE: The mapping of the genome through the TCGA collaborative project recently revealed major intrinsic molecular subtypes, Basal, Luminal, and Neural muscle-invasive urothelial carcinoma (UC), which have shown prognostic and predictive values. A standardized approach in daily practice, which is simple, fast, reproducible, and at low cost has not yet been identified. We provide to test the hypothesis that immuno-phenotypical score classification (Piescore) may discriminate Luminal from Basal from Neural UC, and to find an association of tumor Piescore with histological and clinical prognostic variables in a mono-institutional cohort of muscle-invasive (pT2) UC treated with trans-urethral resection and radical cystectomy (RC). METHODS: Primary endpoint is to stratify Luminal, Basal or Neural tumors according to a simple immuno-phenotypical score. Consecutive transurethral resection specimens harbored foci of high grade, pT2 (MIBC) from 75 pts who subsequently underwent RC, have been submitted for immunohistochemical analysis, using relevant gene-expression-based markers for Basal type (CD44, CK5/6) and Luminal type (CK20 and pPARg). Piescore divided the tumors into Basal and Luminal types when at least 3 of 4 markers were consistent with a specific phenotype. RESULTS: Luminal and Basal phenotype was present in 32 pts and 29 pts (43% and 39% respectively) while in 7 pts (9% of cases) the Piescore indentified a mixed phenotype (when 2 Luminal markers and 2 Basal markers were present simultaneously). No expression was identified in 7 pts (9%): 4 cases (5%) with morphological neuroendocrine differentiation and 3 cases (4%) with classical urothelial differentiation, all consistent with Neural phenotype. Basal Piescore with all markers consistent with basal differentiation (CD44+, CK5/6+, CK20-, pPARg-) was associated with advance stage at cystectomy (pT3-4 vs pT0-1-2, 73% vs 27% of cases respectively). Only necrosis, among histopathological parameters considered, was statistically correlated with Basal phenotype (OR: 3.3, p: 0.030), while no association with lymph-vascular invasion, papillary subtype, primary tumor, and concomitant CIS was found. CONCLUSIONS: Piescore immunophenotyping could be a simple surrogate in alternative to genome profiling, able to stratify UC-TURB patients between Luminal vs Basal type. The basal phenotype identified with immunohistochemical markers CD44, CK5/6, CK20 and pPARg seems to stratify more aggressive UC at cystectomy. Neural Piescore also identified a subset of high-grade carcinomas that harbored classical features of UC at histology. Indeed, the biological significance of the expression of multiple phenotypes in the same UC (Piescore mixed tumors) has to be further evaluate. Further studies are mandatory in order to confirm and extend our finding to clinical utility. Source of Funding: None.