Department of Urology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., J8.130, Dallas, TX, 75390-9110, USA.
Department of Urology, Hacettepe University, Ankara, Turkey.
World J Urol. 2019 Nov;37(11):2419-2427. doi: 10.1007/s00345-019-02678-x. Epub 2019 Feb 13.
To evaluate the prognostic value of BRCA1-associated protein-1 (BAP1) expression in upper tract urothelial carcinoma (UTUC), as BAP1 mutations have been associated with prognostic implications in urologic and non-urologic malignancies.
We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy (RNU) for high-grade UTUC from 1990-2008. Immunohistochemistry (IHC) for BAP1 was performed on tissue microarrays. Staining intensity was graded from 0-3, with BAP1 loss defined as an average intensity of < 1. Clinicopathologic characteristics and oncologic outcomes [recurrencefree (RFS), cancer-specific (CSS), and overall survival (OS)] were stratified by BAP1 status. The prognostic role of BAP1 was assessed using Kaplan-Meier (KM) and Cox regression analysis. Significance was defined as p < 0.05.
348 patients were included for analysis and 173 (49.7%) showed BAP1 loss. Median follow-up was 36.0 months. BAP1 loss was associated with papillary architecture and absence of tumor necrosis or CIS. On univariable analysis, BAP1 loss was associated with improved RFS (HR 0.60, p = 0.013) and CSS (HR 0.55, p = 0.007), although significance was lost on multivariable analysis (HR 0.71, p = 0.115 and HR 0.65, p = 0.071; respectively) after adjusting for other significant parameters. BAP1 expression was not significantly associated with OS.
BAP1 loss was associated with favorable pathologic features and better oncologic outcomes in univariate but not multivariate analysis in patients with high-grade UTUC. In contrast to renal cell carcinoma, loss of BAP1 expression appears to confer a better prognosis in high-grade UTUC. The role of the BAP1 pathway in UTUC pathogenesis remains to be further elucidated.
评估 BRCA1 相关蛋白-1（BAP1）在尿路上皮癌（UTUC）中的表达的预后价值，因为 BAP1 突变与泌尿外科和非泌尿外科恶性肿瘤的预后相关。
我们回顾了 1990 年至 2008 年期间因高级别 UTUC 行根治性肾输尿管切除术（RNU）的多机构患者队列。对组织微阵列进行 BAP1 免疫组织化学（IHC）染色。染色强度从 0 到 3 分级，BAP1 缺失定义为平均强度<1。根据 BAP1 状态分层比较临床病理特征和肿瘤学结果（无复发生存（RFS）、癌症特异性（CSS）和总体生存（OS））。使用 Kaplan-Meier（KM）和 Cox 回归分析评估 BAP1 的预后作用。p<0.05 定义为具有统计学意义。
纳入 348 例患者进行分析，其中 173 例（49.7%）存在 BAP1 缺失。中位随访时间为 36.0 个月。BAP1 缺失与乳头状结构和无肿瘤坏死或 CIS 相关。单变量分析显示，BAP1 缺失与 RFS（HR 0.60，p=0.013）和 CSS（HR 0.55，p=0.007）改善相关，但在多变量分析中失去了意义（HR 0.71，p=0.115 和 HR 0.65，p=0.071；分别），在调整其他显著参数后。BAP1 表达与 OS 无显著相关性。
BAP1 缺失与高级别 UTUC 患者的有利病理特征和更好的肿瘤学结果相关，但在多变量分析中无统计学意义。与肾细胞癌相反，BAP1 表达缺失似乎在高级别 UTUC 中预示着更好的预后。BAP1 通路在 UTUC 发病机制中的作用有待进一步阐明。
