Diagnosis of urinary bladder urothelial carcinoma by immunocytology with p53, MCM5, MCM2 and Ki-67 antibodies using cell blocks derived from urine

Cytopathology. 2019 Sep;30(5):510-518. doi: 10.1111/cyt.12698. Epub 2019 May 20.

Abstract

Objective: Immunocytochemistry has attained a marginal role in urology so far. Combining the morphological and immunophenotypical changes of the urothelial cells retrieved from urine is a logical approach. The study aimed to analyse the diagnostic potential of immunocytological staining in the detection of high-grade and low-grade urothelial carcinoma.

Methods: Freshly voided urine was collected from 152 consecutive individuals, cytology classes were determined and cell blocks produced. A total of 77 patients were diagnosed with urothelial carcinoma and 75 patients had various benign urological conditions. Immunocytochemistry was performed using four antibodies: p53, MCM2, MCM5 and Ki-67. A diagnostic power to detect low grade and high-grade urothelial carcinoma was analysed for each antibody and their combinations with cytology.

Results: There were no significant differences between patients with low-grade tumours and control group. Antibodies p53 and Ki-67 slightly improved the sensitivity of urinary cytology while maintaining its specificity. The best negative predictive value was demonstrated in combinations of cytology and MCM5 (88.9%) and cytology, p53 and MCM5 (90.6%). In the diagnosis of high-grade tumours, all antibodies apart from MCM2 yielded better sensitivity and specificity than cytology alone (receiver operating characteristic curves: p53 = 0.853, MCM5 = 0.931, and Ki-67 = 0.895). Combined with cytology, the sensitivities went even higher for the cost of lower specificity. The best diagnostic performance was observed in the combination of MCM5 and Ki-67 (sensitivity = 96.2%; specificity = 80%).

Conclusions: Immunocytochemistry with p53, MCM5 and Ki-67 antibodies can improve the diagnostic power of urinary cytology in the detection and follow-up of urinary bladder urothelial carcinoma.

Keywords: diagnosis; follow-up; immunocytochemistry; urinary bladder; urinary cell block; urinary cytology; urothelial carcinoma.

MeSH terms

  • Aged
  • Antibodies, Neoplasm / immunology*
  • Biomarkers, Tumor / metabolism
  • Cell Cycle Proteins / immunology*
  • Cytodiagnosis*
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / immunology*
  • Male
  • Minichromosome Maintenance Complex Component 2 / immunology*
  • Neoplasm Grading
  • ROC Curve
  • Sensitivity and Specificity
  • Tumor Suppressor Protein p53 / immunology*
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / pathology
  • Urine / cytology*

Substances

  • Antibodies, Neoplasm
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Ki-67 Antigen
  • MCM5 protein, human
  • Tumor Suppressor Protein p53
  • MCM2 protein, human
  • Minichromosome Maintenance Complex Component 2