仅上尿路尿路上皮癌以及伴有同步或异时性膀胱癌的生物标志物分析

Biomarker Profiling of Upper Tract Urothelial Carcinoma Only and with Synchronous or Metachronous Bladder Cancer.

作者信息

Meireles Sara, Dias Carolina, Martins Diana, Marques Ana, Dias Nuno, Pacheco-Figueiredo Luís, Silva João, Silva Carlos Martins, Barbosa Miguel, Costa Luís, Lopes José Manuel, Soares Paula

机构信息

Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.

Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal.

出版信息

Biomedicines. 2024 Sep 23;12(9):2154. doi: 10.3390/biomedicines12092154.

DOI:10.3390/biomedicines12092154

PMID:39335667

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11429062/

Abstract

BACKGROUND

Molecular profiling in upper tract urothelial carcinoma (UTUC) with synchronous or metachronous urothelial bladder cancer (UBC) is scarce. We intended to assess immunohistochemical (IHC) and genetic differences between UTUC-only and UTUC with synchronous or metachronous UBC (UTUC + UBC) and evaluate the effect of subsequent UBC on the outcome of UTUC patients stratified by luminal-basal subtypes.

METHODS

A retrospective cohort of UTUC was divided into UTUC-only ( = 71) and UTUC + UBC ( = 43). IHC expression of cytokeratin 5/6 (CK5/6), CK20, GATA3, and p53 was evaluated to assess relevant subtypes. Genetic characterization comprised p, , , and status. Kaplan-Meier and Cox regression analyses estimated the effect of clinicopathological variables and molecular profiles on progression-free survival (PFS) and overall survival (OS) of UTUC patients.

RESULTS

No meaningful differences were detected among both subgroups according to luminal-basal stratification and genetic analysis. UTUC + UBC was independently associated with a worse PFS when stratified by luminal-basal phenotype (HR 3.570, CI 95% 1.508-8.453, = 0.004) but with no impact in OS (HR 1.279, CI 95% 0.513-3.190, = 0.597).

CONCLUSIONS

This study reveals that both subgroups exhibited equivalent genomic features and luminal-basal subtypes. The involvement of the bladder relates to shorter PFS but does not seem to influence the survival outcome of UTUC, independently of the IHC phenotype.

摘要

背景

上尿路尿路上皮癌（UTUC）合并同步或异时性膀胱尿路上皮癌（UBC）的分子特征研究较少。我们旨在评估单纯UTUC与合并同步或异时性UBC的UTUC（UTUC + UBC）之间的免疫组化（IHC）和基因差异，并评估后续UBC对按腔-基底亚型分层的UTUC患者预后的影响。

方法

一项UTUC回顾性队列研究分为单纯UTUC组（n = 71）和UTUC + UBC组（n = 43）。评估细胞角蛋白5/6（CK5/6）、CK20、GATA3和p53的IHC表达以评估相关亚型。基因特征包括p16、RB1、FGFR3和TP53状态。Kaplan-Meier和Cox回归分析估计临床病理变量和分子特征对UTUC患者无进展生存期（PFS）和总生存期（OS）的影响。

结果

根据腔-基底分层和基因分析，两个亚组之间未检测到有意义的差异。当按腔-基底表型分层时，UTUC + UBC与较差的PFS独立相关（HR 3.570，95%CI 1.508 - 8.453，P = 0.004），但对OS无影响（HR 1.279，95%CI 0.513 - 3.190，P = 0.597）。