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Basal and Luminal Immunohistochemical Phenotypes in Muscle Invasive Bladder Urothelial Carcinomas (MIBC) Treated with Neoadjuvant Chemotherapy (NAC)

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Sources of Funding: None

Introduction

MIBC patients who respond to cisplatin based NAC, defined as stage

Methods

Pre-treatment tissues from a cohort of 71 NAC treated MIBC patients at our institution between 2000 and 2013 were incorporated in tissue microarray and stained for CK5/6 and GATA3 (Ventana Medical Systems, AZ). Cases were assigned as luminal or basal phenotype based on the extent (70% cut off) of tumor cells with ?2+ staining intensity, Figure 1A. We limited our analysis of CSS to the 40 patient who were able to tolerate ?2 doses of NAC to avoid the confounding effect of patients who were not adequately dosed.

Results

As expected, there was an inverse association for CK5/6 and GATA3: 77% (43/56) of strong GATA3 cases exhibited weak/negative CK5/6 staining, most consistent with the luminal phenotype, and 73% (11/15) of the GATA3 weak/negative cases exhibited strong CK5/6, most consistent with the basal phenotype (Fisher's exact p-value 0.0003). Interestingly there was a ? 2 fold enrichment of basal the phenotype in cases with residual MIBC following NAC, Figure 1B.

Conclusions

Our results suggest a differential responsiveness to NAC for MIBC based on assignment of basal and luminal phenotypes. The current findings should be further evaluated taking P53 gene expression status into account, given previous suggestion of chemotherapy resistance in P53 intact (p53-Like) MIBC. Furthermore, comparison to IHC luminal/basal MIBC phenotypes in our cohort of cystectomy only treated patients is ongoing to help discern the prognostic vs predictive role of this classification for NAC.

Funding

None

Authors
Aline C Tregnago
Maria Del Carmen Rodriguez Pena
Marie-Lisa Eich
Diana Taheri
Hirofumi Nonogaki
Rajni Sharma
David McConkey
Trinity J Bivalacqua
George J Netto
Alexander Baras
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