Urology Unit, Champalimaud Clinical Center, Lisbon, Portugal.
National School of Public Health, Universidade NOVA de Lisboa, Lisbon, Portugal.
Virchows Arch. 2019 Oct;475(4):445-455. doi: 10.1007/s00428-019-02593-x. Epub 2019 Jun 25.
Bladder cancer tumors can be divided into two molecular subtypes referred to as luminal or basal. Each subtype may react differently to current chemotherapy or immunotherapy. Likewise, the technology required for comprehensive molecular analysis is expensive and not yet applicable for routine clinical diagnostics. Therefore, it has been suggested that the immunohistochemical expressions of only two markers, luminal (CK20+, CK5/6-) and basal (CK5/6+, CK20-), is sufficient to identify the molecular subtypes of bladder cancer. This would represent a molecular grade that could be used in daily practice. Molecular classification is done using immunohistochemistry to assess luminal-basal phenotype based on tissular expression of CK20 and CK5/6 as surrogate for luminal or basal subtypes, respectively. A series of 147 non-muscle-invasive bladder carcinoma cases was selected, and the tumors were divided into four subgroups based on the presence of CK20 and/or CK5/6, that is, null (CK20-, CK5/6-), mixed (CK20+, CK5/6+), basal (CK20-, CK5/6+), and luminal (CK20+, CK5/6-) categories. Survival analysis was estimated using the Kaplan-Meier method and the log-rank test. Hazard ratios were calculated by Cox multivariate analysis. The molecular grade included cases with null (n = 89), mixed (n = 6), basal (n = 20), and luminal (n = 32) phenotypes with differences in recurrence-free, progression-free and cancer-specific survival associated with molecular-grade categories in patients with low- or high-grade Ta, or high-grade T1 tumors. The multivariate analysis identified the luminal phenotype as a predictor of more aggressive neoplasms. Our findings provide a rationale to investigate luminal and basal subtypes of bladder cancer using two gene expression signatures as surrogate markers and show that non-muscle-invasive bladder carcinoma can be stratified into biologically and clinically different subgroups by using an immunohistochemical classifier.
膀胱癌肿瘤可分为两种分子亚型，分别称为 luminal 或 basal。每种亚型可能对当前的化疗或免疫疗法有不同的反应。同样，全面分子分析所需的技术昂贵且不适用于常规临床诊断。因此，有人建议仅通过免疫组织化学表达两种标志物，即 luminal（CK20+，CK5/6-）和 basal（CK5/6+，CK20-），就足以鉴定膀胱癌的分子亚型。这将代表一种可在日常实践中使用的分子分级。分子分类是通过免疫组织化学来评估基于 CK20 和 CK5/6 在组织中的表达的 luminal-basal 表型，分别作为 luminal 或 basal 亚型的替代物。选择了一系列 147 例非肌肉浸润性膀胱癌病例，并根据 CK20 和/或 CK5/6 的存在将肿瘤分为四个亚组，即阴性（CK20-，CK5/6-）、混合（CK20+，CK5/6+）、基底（CK20-，CK5/6+）和 luminal（CK20+，CK5/6-）。使用 Kaplan-Meier 方法和对数秩检验估计生存分析。通过 Cox 多变量分析计算危险比。分子分级包括阴性（n=89）、混合（n=6）、基底（n=20）和 luminal（n=32）表型的病例，低级别 Ta 或高级 T1 肿瘤患者的无复发生存、无进展生存和癌症特异性生存与分子分级类别相关。多变量分析确定 luminal 表型是侵袭性更强的肿瘤的预测因子。我们的发现为使用两个基因表达特征作为替代标志物研究膀胱癌的 luminal 和 basal 亚型提供了依据，并表明非肌肉浸润性膀胱癌可以通过免疫组织化学分类器分为生物学和临床不同的亚组。
