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

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Anne Menz ◽  
Timo Weitbrecht ◽  
Natalia Gorbokon ◽  
Franziska Büscheck ◽  
Andreas M. Luebke ◽  
...  
Keyword(s):  
Tissue Microarray ◽  
Squamous Cell ◽  
Renal Cell ◽  
Precursor Cells ◽  
Squamous Cell Carcinomas ◽  
Type I ◽  
Prognostic Impact ◽  
Down Regulation ◽  
Cytokeratin 18 ◽  
Tumor Types

Abstract 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.

scholarly journals Diagnostic and Prognostic Impact of Cytokeratin 18 Expression in Human Tumors: A Tissue Microarray Study on 11,952 Tumors

2020 ◽  
Author(s):  
Anne Menz ◽  
Timo Weitbrecht ◽  
Franziska Büscheck ◽  
Andreas M Luebke ◽  
Martina Kluth ◽  
...  
Keyword(s):  
Tissue Microarray ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Renal Cell ◽  
Precursor Cells ◽  
Squamous Cell Carcinomas ◽  
Intermediate Filament Protein ◽  
Type I ◽  
Prognostic Impact ◽  
Tumor Types

Abstract BackgroundCytokeratin 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. MethodsTo 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. ResultsCK18 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≤0.001) 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. ConclusionsDown-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.

Multiple squamous cell carcinomas following treatment with sorafenib for renal cell carcinoma

2013 ◽  
Vol 52 (12) ◽  
pp. 1538-1541 ◽  
Author(s):  
Abdel Kader El Tal ◽  
Christopher J. Remichofsky ◽  
David A. Mehregan ◽  
Laura K. Ganger
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Renal Cell ◽  
Squamous Cell Carcinomas

Expression and prognostic impact of indoleamine 2,3-dioxygenase in oral squamous cell carcinomas

Oral Oncology ◽  
2011 ◽  
Vol 47 (5) ◽  
pp. 352-357 ◽  
Author(s):  
Klaus Laimer ◽  
Birgit Troester ◽  
Frank Kloss ◽  
Georg Schafer ◽  
Peter Obrist ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Squamous Cell Carcinomas ◽  
Prognostic Impact ◽  
Oral Squamous Cell Carcinomas ◽  
Indoleamine 2,3 Dioxygenase

HIF-1α is a Prognostic Marker in Oral Squamous Cell Carcinomas

2010 ◽  
Vol 25 (2) ◽  
pp. 87-92 ◽  
Author(s):  
Alexander W. Eckert ◽  
Andreas Schütze ◽  
Matthias H.W. Lautner ◽  
Helge Taubert ◽  
Johannes Schubert ◽  
...  
Keyword(s):  
Prognostic Marker ◽  
Squamous Cell ◽  
Squamous Cell Carcinomas ◽  
Immunoperoxidase Technique ◽  
Prognostic Impact ◽  
Disease Specific Survival ◽  
Cox Regression Analysis ◽  
Oral Squamous Cell Carcinomas ◽  
Increased Risk ◽  
Disease Specific

The critical molecular regulator of hypoxia is the hypoxia-inducible factor 1 alpha (HIF-1α). The prognostic impact of this regulator protein in oral squamous cell carcinomas (OSCC) has not been comprehensively investigated. The aim of this study was to analyze the expression of HIF-1α in 82 patients with OSCC and to correlate it with their disease-specific survival. Immunohistochemical staining for HIF-1α was performed on 82 OSCC specimens using a standard immunoperoxidase technique. The expression of HIF-1α was correlated with poor disease-specific survival for OSCC patients. Patients with negatively or weakly HIF-1α–expressing tumors had a survival rate of 80%, whereas the survival decreased to only 33.6% in case of moderate or strong expression. In multivariate Cox regression analysis, we found a 3.5-fold increased risk of tumor-related death when HIF-1α was strongly expressed (p=0.016) compared to negative or weak expression of HIF-1α. We suggest HIF-1α is an independent prognostic marker in OSCC. Immunohistochemical detection of HIF-1α appears to be useful in the diagnosis of OSCC and to provide prognostic information in addition to TNM stage and histological grade.

scholarly journals Decreased Expression of Inhibitor of Caspase-Activated DNase (ICAD) in Renal Cell Carcinoma – Tissue Microarray of Human Samples

2016 ◽  
Vol 3 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Retnagowri Rajandram ◽  
Azad H. A. Razack ◽  
Keng Lim Ng ◽  
Glenda C Gobe
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tissue Microarray ◽  
Renal Cell ◽  
Clear Cell ◽  
Normal Kidney ◽  
Down Regulation ◽  
Caspase Activated Dnase ◽  
Clear Cell Rcc ◽  
Metastatic Rcc

Although primary localised tumours of renal cell carcinoma (RCC) can be treated relatively successfully with surgery, metastatic RCC has poor prognosis because of late diagnosis and resistance to therapies. In the present study, we were interested in profiling the protein expression of “inhibitor of caspase-activated DNase” (ICAD), an apoptosis inhibitor, in kidney cancer and its paired normal kidney. Immunohistochemistry with automated batch staining and morphometry using digital pathology were used to compare ICAD in 121 RCC specimens with their paired normal kidney tissue. Tissue microarray of formalin-fixed, paraffin-embedded archival tissue was used. Intensity and localisation of ICAD were compared between normal and cancer samples, and against grading within the cancers. The results demonstrated that, in this cohort, ICAD was highly expressed in the proximal tubular epithelium of normal kidney, and significantly decreased in clear cell RCC tissue (p < 0.05) as well as other subtypes of RCC (p < 0.01) compared with normal kidney. There was a tendency towards nuclear localisation of ICAD in clear cell RCC, but not in other subtypes of RCC. No significant association was found between ICAD intensity and grade of RCC. In summary, down-regulation of ICAD occurs in RCC. ICAD normally inhibits DNA fragmentation and apoptosis; thus, its down-regulation was unexpected in a cancer known for its resistance to apoptosis. However, these RCC samples were from primary, not metastatic, RCC sites, and down-regulated ICAD may be part of a progressive pathway that promotes RCC metastasis.

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