Tbilisi State Medical University, Georgia.
Georgian Med News. 2021 Jul-Aug(316-317):178-184.
Urothelial carcinoma represents the most common type of bladder cancer (>90%) and is the most frequent malignancy of the urinary tract. Most of the urothelial carcinomas are non-invasive at the time of diagnosis, however they are characterised with the risk of recurrence after surgical treatment. The aim of our study was to investigate the characteristics of tumor heterogeneity and markers of its progression in urothelial papillary carcinomas. Study included following groups: normal urothelial epithelium, urothelial papilloma, urothelial neoplasms with low malignant potential (PUNLM), non-invasive low grade papillary urothelial carcinomas (LGPUC) and non-invasive high grade papillary urothelial carcinomas (HGPUC). In addition, study included relapsed cases of non-invasive LGPUC and HGPUC. Nuclear features and mitotic counts was assessed using digital pathology software QuPath in standard H&E stained specimens. In addition, the presence of mitosis was detected as PHH3 labelled cells by immunohistochemistry. Proliferation was measured as Ki67 labelling index by immunohistochemistry. Tumor heterogeneity was investigated by the differential expression pattern of CK5, CK7 and CK20 by immunohistochemistry. Study results showed, that Nuclear features, as well as the number of mitosis, proliferation index and intratumoral heterogeneity significantly correlate with the presence of higher grade non-invasive urothelial lesions. In addition, it is possible to distinguish two major groups of non-invasive LGPUC and HGPUC, based on nuclear and phenotypic heterogeneity and mitotic and proliferative activity, I group which is characterised with higher intratumoral heterogeneity, higher mitotic count and higher proliferative activity, represents the high risk group of non-invasive LGPUC and HGPUC recurrence.
尿路上皮癌是最常见的膀胱癌类型（>90%），也是泌尿道最常见的恶性肿瘤。大多数尿路上皮癌在诊断时是非浸润性的，但它们具有手术后复发的风险。我们的研究目的是研究尿路上皮乳头状癌的肿瘤异质性特征及其进展标志物。研究包括以下组：正常尿路上皮、尿路上皮乳头瘤、低恶性潜能尿路上皮肿瘤（PUNLM）、非浸润性低级别乳头状尿路上皮癌（LGPUC）和非浸润性高级别乳头状尿路上皮癌（HGPUC）。此外，研究还包括非浸润性 LGPUC 和 HGPUC 的复发病例。使用数字病理学软件 QuPath 在标准 H&E 染色标本中评估核特征和有丝分裂计数。此外，通过免疫组织化学检测 PHH3 标记的细胞来检测有丝分裂的存在。通过免疫组织化学测量 Ki67 标记指数来测量增殖。通过免疫组织化学检测 CK5、CK7 和 CK20 的差异表达模式来研究肿瘤异质性。研究结果表明，核特征、有丝分裂数、增殖指数和肿瘤内异质性与存在高级别非浸润性尿路上皮病变显著相关。此外，根据核和表型异质性以及有丝分裂和增殖活性，可以将非浸润性 LGPUC 和 HGPUC 分为两个主要组，I 组具有更高的肿瘤内异质性、更高的有丝分裂计数和更高的增殖活性，代表非浸润性 LGPUC 和 HGPUC 复发的高风险组。
