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Copper Transporter-CTR1 Expression and Pathological Outcomes in Platinum-treated Muscle-invasive Bladder Cancer Patients. Anticancer Res 2016 Feb;36(2):495-501

Date

02/07/2016

Pubmed ID

26851002

Scopus ID

2-s2.0-84962195660   17 Citations

Abstract

BACKGROUND/AIM: Platinum (Pt)-based neoadjuvant chemotherapy (NAC) is the standard-of-care for muscle-invasive bladder cancer (MIBC). However, the survival benefit with NAC is driven by patients with pathological response at cystectomy. Non-responders are subject to adverse effects of Pt, with delay in definitive treatment. Copper transporter receptor 1 (CTR1) plays an important role in Pt uptake and the level of expression may influence Pt sensitivity. We hypothesized that tumor CTR1 expression correlated with pathological outcome.

PATIENTS AND METHODS: We identified matched paraffin-embedded tissues from pre-NAC transurethral bladder tumor resection (TURBT) and post-NAC radical cystectomy (RC) specimens in 47 patients with MIBC who received Pt-based NAC. Tumor and adjacent normal tissues were stained with CTR1 antibody. CTR1 expression was determined through immunohistochemistry by two pathologists blinded to the outcome (0=undetectable; 1+=barely detectable; 2+=moderate; and 3+=intense staining). Pathological response was defined as either down-staging to non-MIBC (≤pT1N0M0) or complete pathological response (pT0). Pathological outcome was compared between the CTR1 expression groups.

RESULTS: Forty-three percent of TURBT and 41% of RC specimens expressed a CTR1 score of 3+. Forty-four percent of patients had a pathological response to NAC, and 17% had pT0 disease at cystectomy. In both pre-NAC TURBT and post-NAC RC specimens, a CTR1 expression score of 3+ correlated with pathological response (p=0.0076 and p=0.023, respectively).

CONCLUSION: This is the first study to demonstrate a correlation between CTR1 tumor expression and pathological outcome in Pt-treated MIBC. These findings suggest that CTR1 expression may be a biomarker for Pt sensitivity.

Author List

Kilari D, Iczkowski KA, Pandya C, Robin AJ, Messing EM, Guancial E, Kim ES

Authors

Kenneth A. Iczkowski MD Professor in the Pathology department at Medical College of Wisconsin
Deepak Kilari MD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Biomarkers, Tumor
Carcinoma, Squamous Cell
Cation Transport Proteins
Female
Follow-Up Studies
Humans
Immunoenzyme Techniques
Male
Middle Aged
Muscle Neoplasms
Neoadjuvant Therapy
Neoplasm Invasiveness
Neoplasm Staging
Platinum
Prognosis
Urinary Bladder Neoplasms
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