Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; Comprehensive Cancer Center EMN, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Bavarian Center for Cancer Research (BZKF), Erlangen, Germany.
Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; Comprehensive Cancer Center EMN, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Bavarian Center for Cancer Research (BZKF), Erlangen, Germany; Department of Nephropathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Eur Urol Oncol. 2024 Feb;7(1):128-138. doi: 10.1016/j.euo.2023.07.011. Epub 2023 Aug 8.
Grading of muscle-invasive bladder cancer (MIBC) according to the current World Health Organization (WHO) criteria is controversial due to its limited prognostic value. All MIBC cases except a tiny minority are of high grade.
To develop a prognostic histological scoring system for MIBC integrating histomorphological phenotype, stromal tumor-infiltrating lymphocytes (sTILs), tumor budding, and growth and spreading patterns.
DESIGN, SETTING, AND PARTICIPANTS: Tissue specimens and clinical data of 484 patients receiving cystectomy and lymphadenectomy with curative intent with or without adjuvant chemotherapy. Histomorphological phenotypes, sTILs, tumor budding, and growth and spreading patterns were evaluated and categorized into four grade groups (GGs). GGs were correlated with molecular subtypes, immune infiltration, immune checkpoint expression, extracellular matrix (ECM) remodeling, and epithelial-mesenchymal transition (EMT) activity.
GGs were associated with overall (OS), disease-specific (DSS), and progression-free (PFS) survival in univariable and multivariable analyses. Association with biological features was analyzed with descriptive statistics.
Integration of two histomorphological tumor groups, three sTILs groups, three tumor budding groups, and four growth/spread patterns yielded four novel GGs that had high significance in the univariable survival analysis (OS, DSS, and PFS). GGs were confirmed as independent prognostic predictors with the greatest effect in the multivariable Cox regression analysis. Correlation with molecular data showed a gradual transition from basal to luminal subtypes from GG1 to GG4; a gradual decrease in survival, immune infiltration, and immune checkpoint activity; and a gradual increase in ECM remodeling and EMT activity.
We propose a novel, prognostically relevant, and biologically based scoring system for MIBC in cystectomies applicable to routine pathological sections.
We developed a novel approach to assess the aggressiveness of advanced bladder cancer, which allows improved risk stratification compared with the method currently proposed by the World Health Organization.
根据目前的世界卫生组织（WHO）标准对肌层浸润性膀胱癌（MIBC）进行分级存在争议，因为其预后价值有限。除极少数情况外，所有 MIBC 病例均为高级别。
建立一种新的 MIBC 预后组织学评分系统，该系统整合了组织形态学表型、间质肿瘤浸润淋巴细胞（sTILs）、肿瘤芽生和生长及扩散模式。
设计、地点和参与者：对 484 例接受根治性膀胱切除术和淋巴结切除术且接受或未接受辅助化疗的患者的组织标本和临床数据进行评估。评估并将组织形态学表型、sTILs、肿瘤芽生和生长及扩散模式分为四个等级组（GG）。GG 与分子亚型、免疫浸润、免疫检查点表达、细胞外基质（ECM）重塑和上皮-间充质转化（EMT）活性相关。
在单变量和多变量分析中，GG 与总生存（OS）、疾病特异性生存（DSS）和无进展生存（PFS）相关。使用描述性统计方法分析与生物学特征的相关性。
整合两种组织形态学肿瘤组、三种 sTIL 组、三种肿瘤芽生组和四种生长/扩散模式，产生了四个新的 GG，在单变量生存分析（OS、DSS 和 PFS）中具有高显著性。GG 在多变量 Cox 回归分析中被确认为独立的预后预测因子，其影响最大。与分子数据的相关性表明，从 GG1 到 GG4，从基底型向 luminal 型逐渐过渡；生存、免疫浸润和免疫检查点活性逐渐降低；ECM 重塑和 EMT 活性逐渐增加。
我们提出了一种新的、具有预后相关性且基于生物学的 MIBC 评分系统，适用于膀胱切除术的常规病理切片。
我们开发了一种评估晚期膀胱癌侵袭性的新方法，与目前世界卫生组织提出的方法相比，可进行更好的风险分层。
