Diagnostic and prognostic impact of cytokeratin 18 expression in human tumors: a tissue microarray study on 11,952 tumors

TY - JOUR

T1 - Diagnostic and prognostic impact of cytokeratin 18 expression in human tumors: a tissue microarray study on 11,952 tumors

AU - Menz, Anne

AU - Weitbrecht, Timo

AU - Gorbokon, Natalia

AU - Büscheck, Franziska

AU - Luebke, Andreas M

AU - Kluth, Martina

AU - Hube-Magg, Claudia

AU - Hinsch, Andrea

AU - Höflmayer, Doris

AU - Weidemann, Sören

AU - Fraune, Christoph

AU - Möller, Katharina

AU - Bernreuther, Christian

AU - Lebok, Patrick

AU - Clauditz, Till

AU - Sauter, Guido

AU - Uhlig, Ria

AU - Wilczak, Waldemar

AU - Steurer, Stefan

AU - Minner, Sarah

AU - Burandt, Eike

AU - Krech, Rainer

AU - Dum, David

AU - Krech, Till

AU - Marx, Andreas

AU - Simon, Ronald

PY - 2021/2/15

Y1 - 2021/2/15

N2 - BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.

AB - BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.

KW - Biomarkers, Tumor/metabolism

KW - Case-Control Studies

KW - Early Detection of Cancer

KW - Female

KW - Gene Expression Profiling/methods

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Keratin-18/metabolism

KW - Male

KW - Neoplasm Grading

KW - Neoplasms/diagnosis

KW - Prognosis

KW - Survival Analysis

KW - Tissue Array Analysis

U2 - 10.1186/s10020-021-00274-7

DO - 10.1186/s10020-021-00274-7

M3 - SCORING: Journal article

C2 - 33588765

VL - 27

SP - 16

JO - MOL MED

JF - MOL MED

SN - 1076-1551

IS - 1

ER -