Diagnostic and prognostic impact of cytokeratin 18 expression in human tumors: a tissue microarray study on 11,952 tumors
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Diagnostic and prognostic impact of cytokeratin 18 expression in human tumors: a tissue microarray study on 11,952 tumors. / 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.
in: MOL MED, Jahrgang 27, Nr. 1, 15.02.2021, S. 16.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -