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.
Written by:
Piaton E, Advenier AS, Carré C, Decaussin-Petrucci M, Mege-Lechevallier F, Ruffion A. Are you the author?
Hospices Civils de Lyon, Centre de Pathologie Est, Hôpital Femme-Mère-Enfant, Bron Université Claude Bernard Lyon 1, Lyon; Département de Biopathologie, Centre de Lutte Contre le Cancer Léon Bérard, Lyon; Laboratoire MTM France, Jouy en Josas Centre de Pathologie Sud, Centre Hospitalier Lyon; Sud, Pierre Bénite Service d'Anatomie et Cytologie Pathologiques, Hôpital Edouard Herriot, Lyon Service d'Urologie, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
Reference: Cytopathology. 2012 Sep 25. Epub ahead of print.
doi: 10.1111/j.1365-2303.2012.01008.x
PubMed Abstract
PMID: 23003335
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