Abstract：
Cytokeratin 20 (CK20) expression is limited to umbrella cells in the normal urothelium. Since CK20 is often upregulated in neoplastic urothelial cells including dysplasia and carcinoma in situ, immunohistochemical CK20 analysis is often used for the assessment of bladder biopsies. CK20 expression is a feature of luminal bladder cancer subtype, but its prognostic relevance is disputed. In this study, we investigated CK20 on >2700 urothelial bladder carcinomas in a tissue microarray format by immunohistochemistry. Cytoplasmic and membranous CK20 staining was seen in 1319 (51.8%) cancers. The fraction of CK20 positive and especially strongly positive cases increased from pTaG2 low grade (44.5% strongly positive) and pTaG2 high grade (57.7%) to pTaG3 high grade (62.3%; p = 0.0006) but was lower in muscle-invasive (pT2-4) carcinomas (51.1% in all pTa vs. 29.6% in pT2-4; p < 0.0001). Within pT2-4 carcinomas, CK20 positivity was linked to nodal metastasis and lymphatic vessel invasion (p < 0.0001 each) and to venous invasion (p = 0.0177). CK20 staining was unrelated to overall patient survival if all 605 pT2-4 carcinomas were jointly analyzed but subgroup analyses revealed a significant association of CK20 positivity with favorable prognosis in 129 pT4 carcinomas (p = 0.0005). CK20 positivity was strongly linked to the expression of GATA3 (p < 0.0001), another feature of luminal bladder cancer. The combined analysis of both parameters showed best prognosis for luminal A (CK20+/GATA3+, CK20+/GATA3-) and worst outcome for luminal B (CK20-/GATA3+) and basal/squamous (CK20-/GATA3-) in pT4 urothelial carcinomas (p = 0.0005). In summary, the results of our study demonstrate a complex role of CK20 expression in urothelial neoplasms including neoexpression in pTa tumors, a subsequent loss of CK20 expression in a subset of tumors progressing to muscle-invasion, and a stage dependent prognostic role in muscle-invasive cancers.
摘要：
细胞角蛋白20（CK20）的表达仅限于正常尿路上皮中的伞状细胞。由于CK20经常在肿瘤尿路上皮细胞中上调，包括异型增生和原位癌，免疫组织化学CK20分析通常用于评估膀胱活检。CK20表达是腔内膀胱癌亚型的特征，但其预后相关性存在争议。在这项研究中,我们通过免疫组织化学以组织微阵列形式研究了CK20在>2700例膀胱尿路上皮癌中的作用。在1319（51.8％）癌症中可见细胞质和膜CK20染色。CK20阳性和特别是强阳性病例的比例从pTaG2低等级（44.5％强阳性）和pTaG2高等级（57.7％）增加到pTaG3高等级（62.3％；p=0.0006），但在肌肉浸润性（pT2-4）癌中较低（所有pTa的51.1％与在pT2-4中为29.6%；p<0.0001)。在pT2-4癌中，CK20阳性与淋巴结转移和淋巴管浸润（p<0.0001）以及静脉浸润（p=0.0177）有关。如果联合分析所有605pT2-4癌，则CK20染色与患者总生存期无关，但亚组分析显示，在129pT4癌中，CK20阳性与良好预后显着相关（p=0.0005）。CK20阳性与GATA3的表达密切相关（p<0.0001），管腔膀胱癌的另一个特征。两个参数的综合分析显示腔A的最佳预后（CK20/GATA3，CK20/GATA3-）和pT4尿路上皮癌中管腔B（CK20-/GATA3）和基底/鳞状（CK20-/GATA3-）的最差结果（p=0.0005）。总之,我们的研究结果表明CK20表达在尿路上皮肿瘤中的复杂作用，包括在pTa肿瘤中的新表达，随后在一部分肿瘤中CK20表达丧失，进展为肌肉浸润，以及在肌肉浸润性癌症中的阶段依赖性预后作用。
