The coexpression of fibroblast activation protein (FAP) and basal-type markers (CK 5/6 and CD44) predicts prognosis in high-grade invasive urothelial carcinoma of the bladder
The coexpression of fibroblast activation protein (FAP) and basal-type markers (CK 5/6 and CD44) predicts prognosis in high-grade invasive urothelial carcinoma of the bladder
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DOI：
10.1016/j.humpath.2019.07.002
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发表时间：
2019-09-01
期刊：
影响因子：
3.3
通讯作者：
Angulo, Javier C.
中科院分区：
文献类型：
--
作者：
Calvete, Julio;Larrinaga, Gorka;Angulo, Javier C.
高级别膀胱尿路上皮癌是一种预后差的异质性疾病。膀胱肿瘤的基础表型本质上是侵略性的，和形态学参数，确定疾病分期仍然是主要的预测。我们打算评估癌症相关成纤维细胞（CAFs）在膀胱癌预后中的作用及其与基底和管腔表型的关系。临床和病理参数，包括成纤维细胞活化蛋白（FAP）和基础标志物（CK 5/6）的免疫组化表达。CD 44）和lumina]（CK 20，GATA 3）表型，已经在一系列的121例接受根治性膀胱切除术和淋巴结清扫术治疗的膀胱UC患者中进行了研究，并评估了它们在长期癌症特异性生存中的意义。CAF中FAP的胞质免疫染色表明疾病特异性生存率更差（风险比[HR] = 1.68; P = 0.048）。FAP表达与肿瘤分期相关（P < .0001），在T2 a/T2 b水平具有最佳区分度，并且与管腔表型标记物如CK 20（P < .0001）和GATA 3（P = .005）的阴性表达相关。在多变量分析中，FAP、CK 5/6和CD 44的同时表达是疾病特异性生存率的一个强指标（HR = 2.3; P = 0.001），与淋巴结浸润（HR = 3.47; P <0.0001）和膀胱浸润至深部肌肉或更深处（HR = 2.47; P = 0.02）一起。原发肿瘤和淋巴结疾病中FAP阳性表达之间无相关性（P = 0.22）。CAFs中FAP的表达有利于基础表型的高级别浸润性膀胱UC的肿瘤侵袭。这种新的免疫组化标记物可以添加到常规免疫组化方案中，以预测这些患者的临床行为。(C)2019爱思唯尔公司All rights reserved.
High-grade urothelial carcinoma (UC) of the bladder is a heterogeneous disease with dismal prognosis. Bladder tumors with basal phenotype are intrinsically aggressive, and morphological parameters that define disease staging remain main prognosticators. We intend to evaluate the role of cancer-associated fibroblasts (CAFs) in the prognosis of bladder cancer and its association with basal and luminal phenotypes. Clinical and pathological parameters, including the immunohistochemical expression of fibroblast activation protein (FAP) and markers of basal (CK5/6. CD44) and lumina] (CK20, GATA3) phenotypes, have been investigated in a series of 121 patients with UC of the bladder treated by radical cystectomy with lymph node dissection, and their implication in long-term cancer-specific survival has been evaluated. A cytoplasmic immunostaining of FAP in CAFs implies worse disease specific survival (hazard ratio [HR] = 1.68; P = .048). FAP expression is associated with tumor staging (P < .0001), with best discrimination at T2a/T2b level, and with negative expression of markers of luminal phenotype, such as CK20 (P < .0001) and GATA3 (P = .005). In the multivariate analysis, simultaneous expression of FAP, CK5/6, and CD44 is a strong prognosticator of disease-specific survival (HR = 2.3; P = .001), together with nodal invasion (HR = 3.47; P < .0001) and bladder infiltration up to deep muscle or beyond (HR = 2.47; P = .02). There is no association between positive FAP expression in primary tumor and nodal disease (P = .22). FAP expression in CAFs favors tumor invasion in high-grade invasive UC of the bladder with basal phenotype. This new immunohistochemical marker could be added to the routine immunohistochemical protocol to predict clinical behavior in these patients. (C) 2019 Elsevier Inc. All rights reserved.