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p16INK4a/Ki‐67 dual labelling as a marker for the presence of high‐grade cancer cells or disease progression in urinary cytopathology
Authors:A S Advenier  C Carré  M Decaussin‐Petrucci  F Mege‐Lechevallier  A Ruffion
Institution:1. Département de Biopathologie, Centre de Lutte Contre le Cancer Léon Bérard, Lyon;2. Laboratoire MTM France, Jouy en Josas;3. Université Claude Bernard Lyon 1, Lyon;4. Centre de Pathologie Sud, Centre Hospitalier Lyon Sud, Pierre Bénite;5. Service d’Anatomie et Cytologie Pathologiques, H?pital Edouard Herriot, Lyon;6. Service d’Urologie, Centre Hospitalier Lyon Sud, Pierre Bénite, France
Abstract:E. Piaton, A. S. Advenier, C. Carré, M. Decaussin‐Petrucci, F. Mege‐Lechevallier and A. Ruffion
p16 INK4a /Ki‐67 dual labelling as a marker for the presence of high‐grade cancer cells or disease progression in urinary cytopathology Objective: Overexpression of p16INK4a independent of the presence of E6–E7 oncoproteins of high‐risk papillomaviruses has been identified in bladder carcinoma in situ lesions with or without concurrent papillary or invasive high‐grade (HG) urothelial carcinoma. As p16INK4a and Ki‐67 co‐expression clearly indicates deregulation of the cell cycle, the aim of this study was to investigate the frequency of p16INK4a/Ki‐67 dual labelling in urinary cytology samples. Methods: Immunolabelling was performed in demounted, destained Papanicolaou slides after ThinPrep® processing. A total of 84 urinary cytology samples (18 negative, 10 low grade, 19 atypical urothelial cells and 37 high grade) were analysed for p16INK4a/Ki‐67 co‐expression. We assessed underlying urothelial malignancy with cystoscopy, histopathology and follow‐up data in every case. Results: Compared with raw histopathological results, p16 INK4a/Ki‐67 dual labelling was observed in 48 out of 55 (87.3%) HG lesions and in 11 out of 29 (37.9%) negative, papillary urothelial neoplasia of low malignant potential or low‐grade carcinomas (P = 0.05). All cases with high‐grade/malignant cytology were dual labelled. Sixteen out of 17 (94.1%) carcinoma in situ cases and eight out of 14 (57.1%) cases with atypical urothelial cells matching with HG lesions were dual labelled. Extended follow‐up allowed three cases of progression to be diagnosed in dual‐labelled cases with negative/low‐grade cytology results after a 9‐ to 11‐months delay. Conclusions: The data show that p16INK4a/Ki‐67 co‐expression allows most HG cancer cells to be detected initially and in the follow‐up period. Additional studies are needed in order to determine whether dual labelling can be used as a triage tool for atypical urothelial cells in the urine.
Keywords:p16INK4a  Ki‐67  urothelial carcinoma  bladder  liquid‐based cytology  immunocytochemistry
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