Menz Anne, Weitbrecht Timo, Gorbokon Natalia, Büscheck Franziska, Luebke Andreas M, Kluth Martina, Hube-Magg Claudia, Hinsch Andrea, Höflmayer Doris, Weidemann Sören, Fraune Christoph, Möller Katharina, Bernreuther Christian, Lebok Patrick, Clauditz Till, Sauter Guido, Uhlig Ria, Wilczak Waldemar, Steurer Stefan, Minner Sarah, Burandt Eike, Krech Rainer, Dum David, Krech Till, Marx Andreas, Simon Ronald
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany.
Mol Med. 2021 Feb 15;27(1):16. doi: 10.1186/s10020-021-00274-7.
Cytokeratin 18 (CK18) is an intermediate filament protein of the cytokeratin acidic type I group and is primarily expressed in single-layered or "simple" epithelial tissues and carcinomas of different origin.
To systematically determine CK18 expression in normal and cancerous tissues, 11,952 tumor samples from 115 different tumor types and subtypes (including carcinomas, mesenchymal and biphasic tumors) as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format.
CK18 was expressed in normal epithelial cells of most organs but absent in normal squamous epithelium. At least an occasional weak CK18 positivity was seen in 90 of 115 (78.3%) tumor types. Wide-spread CK18 positivity was seen in 37 (31.9%) of tumor entities, including adenocarcinomas of the lung, prostate, colon and pancreas as well as ovarian cancer. Tumor categories with variable CK18 immunostaining included cancer types arising from CK18 positive precursor cells but show CK18 downregulation in a fraction of cases, tumor types arising from CK18 negative precursor cells occasionally exhibiting CK18 neo-expression, tumors derived from normal tissues with variable CK18 expression, and tumors with a mixed differentiation. CK18 downregulation was for example seen in renal cell cancers and breast cancers, whereas CK18 neo-expression was found in squamous cell carcinomas of various origins. Down-regulation of CK18 in invasive breast carcinomas of no special type and clear cell renal cell carcinomas (ccRCC) was related to adverse tumor features in both tumors (p ≤ 0.0001) and poor patient prognosis in ccRCC (p = 0.0088). Up-regulation of CK18 in squamous cell carcinomas was linked to high grade and lymph node metastasis (p < 0.05). In summary, CK18 is consistently expressed in various epithelial cancers, especially adenocarcinomas.
Down-regulation or loss of CK18 expression in cancers arising from CK18 positive tissues as well as CK18 neo-expression in cancers originating from CK18 negative tissues is linked to cancer progression and may reflect tumor dedifferentiation.
细胞角蛋白18（CK18）是细胞角蛋白酸性I型组的一种中间丝蛋白，主要表达于单层或“简单”上皮组织以及不同起源的癌组织中。
为系统地确定CK18在正常组织和癌组织中的表达情况，采用组织芯片技术，通过免疫组织化学方法分析了来自115种不同肿瘤类型和亚型（包括癌、间叶组织肿瘤和双相肿瘤）的11952个肿瘤样本以及76种不同正常组织类型的608个样本。
CK18在大多数器官的正常上皮细胞中表达，但在正常鳞状上皮中不表达。在115种肿瘤类型中的90种（78.3%）中至少偶尔可见弱CK18阳性。在37种（31.9%）肿瘤实体中可见广泛的CK18阳性，包括肺癌、前列腺癌、结肠癌、胰腺癌以及卵巢癌。CK18免疫染色变化的肿瘤类别包括源自CK18阳性前体细胞但部分病例显示CK18下调的癌症类型、源自CK18阴性前体细胞偶尔表现出CK18新表达的肿瘤类型、源自CK18表达可变的正常组织的肿瘤以及具有混合分化的肿瘤。例如，在肾细胞癌和乳腺癌中可见CK18下调，而在各种起源的鳞状细胞癌中发现CK18新表达。在非特殊类型浸润性乳腺癌和透明细胞肾细胞癌（ccRCC）中，CK18下调与两种肿瘤的不良肿瘤特征相关（p≤0.0001），在ccRCC中与患者预后不良相关（p = 0.0088）。鳞状细胞癌中CK18上调与高级别和淋巴结转移相关（p < 0.05）。总之，CK18在各种上皮癌中持续表达，尤其是腺癌。
源自CK18阳性组织的癌症中CK18表达下调或缺失以及源自CK18阴性组织的癌症中CK18新表达与癌症进展相关，可能反映肿瘤去分化。
