Golijanin Borivoj, Gershman Boris, De Souza Andre, Kott Ohad, Carneiro Benedito A, Mega Anthony, Golijanin Dragan J, Amin Ali
Department of Pathology and Laboratory Medicine, The Miriam Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, United States.
Urology Department, Minimally Invasive Urology Institute, The Miriam Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, United States.
Front Oncol. 2021 Apr 22;11:651754. doi: 10.3389/fonc.2021.651754. eCollection 2021.
Small cell carcinoma of the urinary tract (SCCUT) is a rare finding with poor clinical course. This study sheds light on the molecular subtype and identifies risk factors in patients diagnosed with SCCUT. Immunohistochemical expression of immunotherapy target programmed death ligand 1 (PD-L1) and luminal (GATA3), basal (p63), and p53 markers are assessed in patients diagnosed with SCCUT. Univariate analysis identified risk factors. Overall survival (OS) is computed using the Kaplan-Meier method. Tissue was available for 70.2% (33/47). All showed a high PD-L1 expression phenotype. p53 is seen in 93.9% (31/33), mostly as overexpression, GATA3 in 45.5% (15/33), and p63 in 57.6% (19/33). For the entire cohort ( = 47), 1-year survival was 59.6%, and the median OS was 17 months. Univariate analysis shows that chemotherapy [hazard ratio (HR) = 0.29, 95% confidence interval (CI) = 0.14-0.61, = 0.001], radical surgery (HR = 0.37, 95% CI = 0.18-0.76, = 0.007), and diagnosis of non-pure SCCUT (HR = 0.44, 95% CI = 0.22-0.86, = 0.02) are favorable prognostic features. Metastasis had negative associations with survival (HR = 2.1, 95% CI = 1.1-4.2, = 0.03). In this series, pure and mixed SCCUT are characterized by p53 overexpression and a high PD-L1 phenotype. Histology of non-pure SCCUT is a positive prognosticator, and radical cystectomy or chemotherapy can improve OS. These findings demonstrate that SCCUT may be eligible for PD-L1 immunotherapy.
泌尿道小细胞癌（SCCUT）是一种罕见的疾病，临床病程较差。本研究揭示了其分子亚型，并确定了诊断为SCCUT患者的危险因素。对诊断为SCCUT的患者评估免疫治疗靶点程序性死亡配体1（PD-L1）以及管腔型（GATA3）、基底型（p63）和p53标志物的免疫组化表达。单因素分析确定了危险因素。采用Kaplan-Meier法计算总生存期（OS）。70.2%（33/47）的患者有可用组织。所有患者均表现出高PD-L1表达表型。93.9%（31/33）的患者检测到p53，大多为过表达；45.5%（15/33）的患者检测到GATA3；57.6%（19/33）的患者检测到p63。对于整个队列（n = 47），1年生存率为59.6%，中位OS为17个月。单因素分析显示，化疗[风险比（HR）= 0.29，95%置信区间（CI）= 0.14 - 0.61，P = 0.001]、根治性手术（HR = 0.37，95% CI = 0.18 - 0.76，P = 0.007）以及非纯SCCUT的诊断（HR = 0.44，95% CI = 0.22 - 0.86，P = 0.02）是有利的预后特征。转移与生存呈负相关（HR = 2.1，95% CI = 1.1 - 4.2，P = 0.03）。在本系列研究中，纯SCCUT和混合性SCCUT的特征为p53过表达和高PD-L1表型。非纯SCCUT的组织学表现是一个积极的预后指标，根治性膀胱切除术或化疗可改善OS。这些发现表明，SCCUT可能适合接受PD-L1免疫治疗。
