Department of Urology, Clinical Sciences Malmö, Skåne University Hospital, Lund University, Malmö, Sweden.
Department of Urology, Clinical Sciences Malmö, Skåne University Hospital, Lund University, Malmö, Sweden.
Eur Urol. 2015 Nov;68(5):824-32; discussion 835-6. doi: 10.1016/j.eururo.2015.02.021. Epub 2015 Mar 11.
One third of patients with stage T1 urothelial carcinoma (UC) progress to muscle-invasive disease requiring radical surgery. Thus, reliable tools are needed for risk stratification of stage T1 UC.
To investigate the extent to which stratification of stage T1 tumours into previously described molecular pathologic UC subtypes can provide improved information on tumour progression.
DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort of 167 primary stage T1 UCs was characterised by immunohistochemistry and classified into the molecular subtypes urobasal (Uro, 32%), genomically unstable (GU, 58%), and squamous-cell-carcinoma-like (SCCL, 10%).
Progression-free survival using univariate and multivariate models.
Subtype classification was validated using nine additional markers with known subtype-specific expression. Analysis of mRNA expression of progression biomarkers revealed a strong association with molecular subtype. Kaplan-Meier analyses showed that the risk of progression was low for Uro tumours and high for GU/SCCL tumours. High progression risk scores were found only for GU/SCCL tumours. Clinical risk factors such as multifocality, concomitant carcinoma in situ, invasion depth, lymphovascular invasion, and high CD3(+) lymphocyte infiltration were observed almost exclusively in GU/SCCL cases.
Molecular subtypes Uro, GU, and SCCL were identified in an independent population-based cohort of stage T1 UCs. Biomarkers and clinical risk factors for progression were associated with molecular subtype. Rapidly progressing T1 tumours were of subtype GU or SCCL and had either a high progression risk score or an elevated CD3(+) cell count.
We show that classification of stage T1 urothelial carcinoma into molecular subtypes can improve the identification of patients with progressing tumours.
三分之一的 T1 期尿路上皮癌（UC）患者会进展为需要根治性手术的肌层浸润性疾病。因此，需要可靠的工具来对 T1 期 UC 进行风险分层。
研究将 T1 期肿瘤分为先前描述的分子病理 UC 亚型的程度，能否为肿瘤进展提供更多信息。
设计、设置和参与者：本研究为基于人群的队列研究，共纳入 167 例原发性 T1 期 UC 患者，通过免疫组织化学方法进行分类，并分为尿路上皮型（Uro，32%）、基因组不稳定型（GU，58%）和鳞状细胞癌样型（SCCL，10%）。
使用单变量和多变量模型评估无进展生存率。
使用已知具有特定亚型表达的九个额外标志物验证了亚型分类。对进展生物标志物的 mRNA 表达分析显示，与分子亚型具有很强的相关性。Kaplan-Meier 分析显示，Uro 肿瘤的进展风险较低，GU/SCCL 肿瘤的进展风险较高。仅在 GU/SCCL 肿瘤中发现高进展风险评分。高进展风险评分仅见于 GU/SCCL 肿瘤。临床危险因素，如多灶性、同时存在原位癌、浸润深度、脉管浸润和高 CD3(+)淋巴细胞浸润，几乎仅见于 GU/SCCL 病例。
在独立的基于人群的 T1 期 UC 队列中鉴定出 Uro、GU 和 SCCL 三种分子亚型。进展的生物标志物和临床危险因素与分子亚型相关。进展迅速的 T1 期肿瘤为 GU 或 SCCL 亚型，要么具有高进展风险评分，要么具有高 CD3(+)细胞计数。
我们表明，将 T1 期尿路上皮癌分为分子亚型可提高对进展性肿瘤患者的识别能力。
