Piaton E, Advenier A S, Carré C, Decaussin-Petrucci M, Mege-Lechevallier F, Ruffion A
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.
Cytopathology. 2013 Oct;24(5):327-34. doi: 10.1111/j.1365-2303.2012.01008.x. Epub 2012 Sep 25.
Overexpression of p16(INK4a) 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 p16(INK4a) and Ki-67 co-expression clearly indicates deregulation of the cell cycle, the aim of this study was to investigate the frequency of p16(INK4a) /Ki-67 dual labelling in urinary cytology samples.
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 p16(INK4a) /Ki-67 co-expression. We assessed underlying urothelial malignancy with cystoscopy, histopathology and follow-up data in every case.
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.
The data show that p16(INK4a) /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.
在伴有或不伴有同时发生的乳头状或浸润性高级别（HG）尿路上皮癌的原位膀胱癌病变中，已发现p16（INK4a）的过表达与高危乳头瘤病毒E6-E7癌蛋白的存在无关。由于p16（INK4a）和Ki-67共表达清楚地表明细胞周期失调，本研究的目的是调查尿细胞学样本中p16（INK4a）/Ki-67双重标记的频率。
在ThinPrep（®）处理后的脱片、脱色巴氏染色玻片上进行免疫标记。总共84份尿细胞学样本（18份阴性、10份低级别、19份非典型尿路上皮细胞和37份高级别）被分析p16（INK4a）/Ki-67共表达情况。我们对每个病例通过膀胱镜检查、组织病理学和随访数据评估潜在的尿路上皮恶性肿瘤。
与原始组织病理学结果相比，55例HG病变中有48例（87.3%）观察到p16（INK4a）/Ki-67双重标记，29例阴性、低恶性潜能乳头状尿路上皮肿瘤或低级别癌中有11例（37.9%）观察到（P = 0.05）。所有高级别/恶性细胞学病例均为双重标记。17例原位癌病例中有16例（94.1%）以及14例与HG病变匹配的非典型尿路上皮细胞病例中有8例（57.1%）为双重标记。延长随访期后，在双重标记且细胞学结果为阴性/低级别病例中，9至11个月延迟后诊断出3例进展病例。
数据表明，p16（INK4a）/Ki-67共表达能够在初始阶段和随访期检测到大多数HG癌细胞。需要进一步研究以确定双重标记是否可作为尿液中非典型尿路上皮细胞的分流工具。
