Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Department of Urology, All India Institute of Medical Sciences, New Delhi, India.
Ann Diagn Pathol. 2019 Dec;43:151397. doi: 10.1016/j.anndiagpath.2019.08.001. Epub 2019 Aug 3.
Genomic studies have delineated distinct molecular subgroups of urothelial carcinomas whose prognostic impact extends beyond traditional stage and grade groupings. The 'basal' subgroup shows increased gene expression levels of KRT5, KRT6, and KRT14 and low expression levels of GATA binding protein 3, and is associated with an extremely poor outcome. Identification of this subset is necessary for improved patient management and research on targeted therapies. We aimed to assess the prognostic utility of immunohistochemistry (IHC) for basal markers: cytokeratin 5/6 (CK5/6) and 14 (CK14), and luminal markers: cytokeratin 20 (CK20) and Gata3 in muscle invasive urothelial carcinomas (MIBC).
Study was of retrospective design (2014-2017). All chemotherapy naïve patients of MIBC undergoing radical cystectomy were included. IHC was performed on formalin fixed paraffin-embedded whole tumor sections.
Among 40 cases of MIBC included, 45% (18/40) were positive for one or both basal markers, 37.5% (15/40) were positive for one or both luminal markers, while 15% (6/40) were positive for both basal and luminal markers. One case did not express any of the four markers. MIBCs expressing only basal markers presented at an advanced stage with frequent squamous differentiation and showed a trend towards shorter overall survival. Gata3+ MIBCs showed the best outcome irrespective of expression of other markers, while CK14+/Gata3- MIBCs were associated with worst outcomes. Gata3-/CK14- MIBCs showed intermediate survival outcomes. CK5/6, CK20 and p53 expression did not significantly correlate with outcome.
IHC for Gata-3 and CK14 stratified MIBC into distinct prognostic subsets.
基因组研究已经描绘了尿路上皮癌的不同分子亚群，其预后影响超出了传统的分期和分级分组。“基底”亚群显示出 KRT5、KRT6 和 KRT14 的基因表达水平增加，而 GATA 结合蛋白 3 的表达水平降低，并且与极差的预后相关。识别这一部分对于改善患者管理和靶向治疗的研究是必要的。我们旨在评估免疫组织化学（IHC）在基底标志物中的预后效用：细胞角蛋白 5/6（CK5/6）和 14（CK14），以及腔标志物：细胞角蛋白 20（CK20）和 Gata3 在肌层浸润性尿路上皮癌（MIBC）中的应用。
本研究为回顾性设计（2014-2017 年）。所有接受根治性膀胱切除术的 MIBC 化疗初治患者均被纳入。在福尔马林固定石蜡包埋的整个肿瘤切片上进行 IHC。
在 40 例 MIBC 中，45%（18/40）为一个或两个基底标志物阳性，37.5%（15/40）为一个或两个腔标志物阳性，而 15%（6/40）为基底和腔标志物均阳性。1 例未表达这四个标志物中的任何一个。仅表达基底标志物的 MIBC 分期较晚，常伴有鳞化分化，且总生存期较短。Gata3+ MIBC 无论其他标志物表达如何，均显示出最佳结局，而 CK14+/Gata3- MIBC 与最差结局相关。Gata3-/CK14- MIBC 显示出中间生存结果。CK5/6、CK20 和 p53 的表达与结局无显著相关性。
Gata-3 和 CK14 的 IHC 将 MIBC 分为不同的预后亚群。
