Detection and Clinical Significance of Circulating Tumor Cells in Patients Undergoing Radical Cystectomy for Urothelial Bladder Cancer

Clin Genitourin Cancer. 2017 Aug;15(4):455-462. doi: 10.1016/j.clgc.2016.11.005. Epub 2016 Dec 1.

Abstract

Introduction: Estimation of prognosis is patients undergoing radical cystectomy is often unreliable, as occult disease remains undetected by conventional diagnostic tools. The purpose of this study was to evaluate the feasibility and the clinical significance of a polymerase chain reaction assay to detect cytokeratin 7 (CK7) mRNA expression in peripheral blood cells of patients undergoing radical cystectomy for clinically nonmetastatic bladder cancer.

Patients and methods: From 2005 to 2009, 59 patients undergoing radical cystectomy and pelvic lymph node dissection were prospectively investigated. Peripheral blood was collected prior to surgery, and a nested polymerase chain reaction assay was developed to identify patients with circulating cells expressing CK7 mRNA. Preoperative, histopathologic data and clinical outcome were compared with CK7 findings.

Results: CK7 expression was detected in 23 (38.9%) of 59 patients and correlated to T stage and lymph node status. After a median follow-up of 42 months, 29 patients experienced a recurrence, whereas 36 died. The presence of CK7-positive cells was significantly associated with an increased risk for recurrence and decreased survival as compared with patients who were CK7-negative (P < .001 and P < .001, respectively; hazard ratios of 8.77 and 5.2 for recurrence and overall death, respectively). The detection of CK7-positive cells was an independent predictor of recurrence and death in a multivariable analysis.

Conclusion: The detection of CK7 mRNA in the circulating cells of patients undergoing radical cystectomy for urothelial cancer identifies those with significantly increased risk of cancer recurrence and death.

Keywords: Cytokeratin 7; Metastases; Occult disease; Prognosis; Urothelial cancer.

MeSH terms

  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / surgery*
  • Cystectomy / methods*
  • Feasibility Studies
  • Female
  • Humans
  • Keratin-7 / blood
  • Keratin-7 / genetics*
  • Lymph Node Excision
  • Male
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / pathology*
  • Pelvis
  • Prognosis
  • Prospective Studies
  • Survival Analysis
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery*

Substances

  • Biomarkers, Tumor
  • KRT7 protein, human
  • Keratin-7