p16^INK4a overexpression and p16/Ki‐67 dual labeling versus conventional urinary cytology in the evaluation of urothelial carcinoma

Abstract

BACKGROUND: Taking into consideration the known overexpression of p16 INK4a in histologically demonstrated high-grade urothelial malignancies, the objective of the current study was to examine the value of p16 INK4a 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). 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 5.8), 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;122:211-20.

Low prevalence of HPV detection and genotyping in non-muscle invasive bladder cancer using single-step PCR followed by reverse line blot

“…Interestingly, p16INK4a overexpression is common in different histological subtypes of bladder cancer including adenocarcinoma (67 %), urothelial carcinoma with squamous differentiation (45.7 %), high-grade urothelial cancers (85.9 %) and urothelial CIS (92.6 %). However, contrary to gynecological tumors, p16INK4a is not a surrogate marker for evidence of HPV infection in bladder cancer [6,[16][17][18].…”

The combined application of urinary liquid‐based cytology with fluorescence in situ hybridization and p16/Ki‐67 dual immunostaining is valuable for improving the early diagnosis of upper tract urothelial carcinomas

“…p16/Ki‐67 dual labeling appears more sensitive in the detection of high‐grade cervical intraepithelial neoplasia of grade 2 or higher in women with atypical squamous cells of undetermined significance (ASC‐US) or low‐grade squamous intraepithelial lesions (LSILs) . 79.2% high‐grade urothelial tumors and 92.8% high‐grade intraurothelial lesions have been reported to be dual‐labeled with p16/Ki‐67 . When applied to the search for high‐grade urothelial tumors, p16/Ki‐67 dual labeling demonstrated comparable performance to urinary cytology .…”

“…Human p16INK4a (p16) protein is the product of the cyclin‐dependent kinase inhibitor 2A (CDKN2a) gene, which is located on chromosome 9p21. The overexpression of p16 has been reported in urothelial carcinomas . Ki‐67 is a marker of cell proliferation .…”

Expression of p16 and Survivin in gliomas and their correlation with cell proliferation

“…The present study also demonstrated that the expression of Survivin was positively correlated with p16, which suggested that the expression of Survivin may be regulated by p16. It has been established that the overexpression of Survivin and p16 is associated with the malignant transformation of a number of tumors (27,28).…”