Introduction

The Cancer Genome Atlas (TCGA) collaboration has identified two intrinsic subtypes (basal and luminal) in urothelial bladder carcinoma. However, the study was limited to muscle invasive bladder cancer (MIBC). Subsequent studies suggested a limited panel of immunohistochemical markers could be used to assign basal vs luminal phenotype in MIBC with potential prognostic role. In this study we assess the applicability of the proposed phenotype classification in non-muscle invasive bladder cancer (NMIBC).

Methods

Three TMAs were constructed from 165 TURB specimens of 52 bladder cancer patients treated at one of author's institution (1998-2008). Follow up data on recurrence, grade or stage progression were obtained. Immunohistochemistry was performed using automated Ventana System for markers indicative of luminal (GATA3, CK20, ER, uroplakin, HER2/neu) and basal phenotype (CK5/6 and CD44). The extent, intensity and pattern of expression were evaluated for all markers by 3 urologic pathologists. HER2/neu was assessed using the breast and stomach scoring systems.

Results

By univariate analysis, using mean extent of expression as a cut off, higher proportion (83%; p=0.002) of tumors with stage progression demonstrated high CK5/6 expression. 15/143 (10.4%) of tumors with high CK5/6 expression demonstrated a higher stage on subsequent biopsy compared to 3/176 (1.7%) of those with low CK5/6. Higher proportion of tumors with stage progression had low levels of CK20 (75%;p=0.03) and CD44 (66%;p=0.009)._x000D_ Regarding recurrence, higher proportion of tumors with recurrence had low expression levels of CK5/6 (64%), CD44 (53%) and ER (91%) and high HER2/neu expression (53%) (p?0.002). There was no association between the rate of expression of any of the markers and grade progression upon recurrence.

Conclusions

Our findings suggest that both high CK5/6 and low CK20 expression are associated with higher likelihood of stage progression in NMIBC. Further analysis of potential role of basal and luminal markers, individually or in combination, in the prognostication of NMIBC in the context of known clinicopathologic parameters is needed.

Funding

None