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Keywords:

  • p16INK4a;
  • Ki-67;
  • urothelial carcinoma;
  • bladder;
  • prognosis;
  • follow-up

BACKGROUND

Taking into consideration the known overexpression of p16INK4a in histologically demonstrated high-grade urothelial malignancies, the objective of the current study was to examine the value of p16INK4a overexpression and of p16/Ki-67 dual labeling versus urinary cytology in the detection of urothelial lesions.

METHODS

Immunolabeling was performed on demounted and destained Papanicolaou slides after liquid-based ThinPrep processing. Actual diagnoses were ascertained by cystoscopy controls and histopathology. Negative cases, papillary urothelial neoplasia of low malignant potential/low-grade tumor, and high-grade lesions were considered separately.

RESULTS

A total of 216 urine samples were collected from new patients with symptoms who were referred for cystoscopy (92 cases) or patients who were being followed after conservative treatment for lesions involving the bladder (117 cases) or the upper urinary tract (7 cases). p16INK4a positivity was assessed in 171 of the 216 cases (79.2%) and in 93 of 99 high-grade cases with positive cytology (93.9%). Coexpression of p16/Ki-67 in the same cells was observed in 119 of 216 cases (55.1%) and was noted in 18 of 51 cases of negative or papillary urothelial neoplasia of low malignant potential/low-grade tumor (35.3%) and in 80 of 101 high-grade tumors (79.2%) (P < .0001). Thirteen of 14 high-grade intraurothelial lesions (92.8%) were dual labeled. When high-grade tumors, disease progression (increased grade, muscle infiltration, and extension into the upper urinary tract), and cancer-related death were grouped together as an endpoint, dual labeling demonstrated a sensitivity that was slightly higher than that of urinary cytology (82.5% vs 80.8%; P = .8), with 94.9% overall specificity.

CONCLUSIONS

When applied to the search for high-grade and aggressive disease, p16/Ki-67 dual labeling and urinary cytology appear to demonstrate comparable performance. Cancer (Cancer Cytopathol) 2014;122:211–220. © 2013 American Cancer Society.