Department of Pathology, University of British Columbia, Vancouver, Canada.
Department of Urologic Sciences, University of British Columbia, Vancouver, Canada.
Urol Oncol. 2021 May;39(5):301.e17-301.e28. doi: 10.1016/j.urolonc.2021.01.021. Epub 2021 Feb 7.
We evaluated the prognostic value of 10 putative tumor markers by immunohistochemistry in a large multi-institutional cohort of patients with locally advanced urothelial cancer of the bladder (UCB) with the aim to validate their clinical value and to harmonize protocols for their evaluation.
Primary tumor specimens from 576 patients with pathologic (p)T3 UCB were collected from 24 institutions in North America and Europe. Three replicate 0.6-mm core diameter samples were collected for the construction of a tissue microarray (TMA). Immunohistochemistry (IHC) for 10 previously described tumor markers was performed and scored at 3 laboratories independently according to a standardized protocol. Associations between marker positivity and freedom from recurrence (FFR) or overall survival (OS) were analyzed separately for each individual laboratory using Cox regression analysis.
The overall agreement of the IHC scoring among laboratories was poor. Correlation among the 3 laboratories varied across the 10 markers. There was generally a lack of association between the individual markers and FFR or OS. The number of altered cell cycle regulators (p53, Rb, and p21) was associated with increased risk of cancer recurrence (P < 0.032). There was no clear pattern in the relationship between the percentage of markers altered in an 8-marker panel and FFR or OS.
This large international TMA of locally advanced (pT3) UCB suggests that altered expression of p53, Rb, and p21 is associated with worse outcome. However this study also highlights limitations in the reproducibility of IHC even in the most expert hands.
我们通过免疫组织化学评估了 10 种假定肿瘤标志物在一个大型的、多机构的局部晚期膀胱癌患者队列中的预后价值，目的是验证它们的临床价值，并协调其评估方案。
从北美和欧洲的 24 个机构收集了 576 例病理（p）T3 膀胱癌患者的原发肿瘤标本。为构建组织微阵列（TMA），采集了 3 个重复的 0.6 毫米直径核心样本。根据标准化方案，在 3 个实验室独立进行了 10 种先前描述的肿瘤标志物的免疫组织化学（IHC）检测和评分。分别使用 Cox 回归分析，在每个单独的实验室中分析标志物阳性与无复发生存（FFR）或总生存（OS）之间的关系。
实验室之间的 IHC 评分总体一致性较差。3 个实验室之间的相关性因 10 个标志物而异。个体标志物与 FFR 或 OS 之间通常没有关联。细胞周期调节因子（p53、Rb 和 p21）的改变数量与癌症复发的风险增加相关（P<0.032）。在 8 个标志物组合中改变的标志物百分比与 FFR 或 OS 之间没有明确的关系。
这项对局部晚期（pT3）膀胱癌的大型国际 TMA 研究表明，p53、Rb 和 p21 的表达改变与预后不良相关。然而，这项研究也突出了即使在最有经验的手中，IHC 的可重复性也存在局限性。
