Copper transporter-CTR1 expression and pathological outcomes in platinum-treated muscle-invasive bladder cancer patients

Deepak Kilari, Kenneth A. Iczkowski, Chintan Pandya, Adam J. Robin, Edward M. Messing, Elizabeth Guancial, Eric S. Kim

Research output: Contribution to journalArticlepeer-review

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 downstaging 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.

Original languageEnglish (US)
Pages (from-to)495-502
Number of pages8
JournalAnticancer research
Volume36
Issue number2
StatePublished - Feb 2016
Externally publishedYes

Keywords

  • Copper
  • CTR
  • Muscle-invasive bladder cancer
  • Platinum
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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