Warrick Joshua I, Kaag Matthew, Raman Jay D, Chan Wilson, Tran Truc, Kunchala Sudhir, Shuman Lauren, DeGraff David, Chen Guoli
Department of Pathology, Penn State University College of Medicine and Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA.
Department of Surgery, Division of Urology, Penn State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, USA.
Virchows Arch. 2017 Sep;471(3):337-345. doi: 10.1007/s00428-017-2190-3. Epub 2017 Jul 18.
Invasive bladder cancer is diverse, and includes several named histomorphologies that differ from conventional urothelial carcinoma, termed "histologic variants." By transcriptional analysis, bladder cancers can be divided into luminal and basal subtypes. In this paper, we study associations between markers of transcriptional subtypes and variant histology in a retrospective cohort of 309 cystectomy specimens. Histology slides were methodically reviewed for all cases, and variant histology was documented. Immunohistochemistry for FOXA1 (luminal marker) and CK14 (basal maker) was performed on histologic variants and their associated conventional urothelial carcinomas. Invasive carcinoma was present in 270 of the cystectomy specimens, 35% of which contained a histologic variant. Squamous carcinomas expressed higher CK14 levels than micropapillary, nested, and plasmacytoid carcinomas (p < 0.001, Kruskal-Wallis), keeping with the basal character of squamous carcinoma. Likewise, squamous carcinomas expressed lower FOXA1 levels than micropapillary, nested, and plasmacytoid carcinomas (p < 0.001, Kruskal-Wallis), keeping with the luminal character of micropapillary carcinoma, and suggesting that nested and plasmacytoid cancers have luminal character. FOXA1 was expressed at lower levels in conventional urothelial carcinoma associated with squamous carcinoma than conventional urothelial carcinoma associated with micropapillary carcinoma (p = 0.0072, Wilcoxon rank sum). CK14 expression did not differ between conventional urothelial carcinomas associated with squamous versus micropapillary carcinoma (p = 0.89, Wilcoxon rank sum). Instead, CK14 expression was higher in squamous carcinoma than conventional urothelial carcinoma present in the same bladder (p = 0.014, Wilcoxon rank sum, paired). Overall, the findings show that squamous and micropapillary cancers have different expression patterns of CK14 and FOXA1 and suggest that they arise from distinct precursors.
浸润性膀胱癌具有多样性，包括几种命名的组织形态学类型，它们不同于传统尿路上皮癌，被称为“组织学变体”。通过转录分析，膀胱癌可分为腔面型和基底型亚型。在本文中，我们在一个包含309例膀胱切除术标本的回顾性队列中研究转录亚型标志物与组织学变体之间的关联。对所有病例的组织学切片进行了系统回顾，并记录了组织学变体情况。对组织学变体及其相关的传统尿路上皮癌进行了FOXA1（腔面标志物）和CK14（基底标志物）的免疫组织化学检测。270例膀胱切除术标本中存在浸润性癌，其中35%含有组织学变体。鳞状细胞癌的CK14水平高于微乳头癌、巢状癌和浆细胞样癌（p<0.001，Kruskal-Wallis检验），这与鳞状细胞癌的基底特征相符。同样，鳞状细胞癌的FOXA1水平低于微乳头癌、巢状癌和浆细胞样癌（p<0.001，Kruskal-Wallis检验），这与微乳头癌的腔面特征相符，并表明巢状癌和浆细胞样癌具有腔面特征。与微乳头癌相关的传统尿路上皮癌相比，与鳞状细胞癌相关的传统尿路上皮癌中FOXA1表达水平较低（p = 0.0072，Wilcoxon秩和检验）。与鳞状细胞癌和微乳头癌相关的传统尿路上皮癌之间CK14表达无差异（p = 0.89，Wilcoxon秩和检验）。相反，鳞状细胞癌中的CK14表达高于同一膀胱中的传统尿路上皮癌（p = 0.014，Wilcoxon秩和检验，配对）。总体而言，研究结果表明鳞状细胞癌和微乳头癌具有不同的CK14和FOXA1表达模式，并提示它们起源于不同的前体。
