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Cytokeratin 5 and cytokeratin 20 inversely correlate with tumour grading in Ta non-muscle-invasive bladder cancer
Authors:Tim Muilwijk  Murat Akand  Frank Van der Aa  Vincent De Coninck  Marc Claessens  Robert Hente  Markus Eckstein  Yves Allory  Louis Libbrecht  Steven Joniau  Thomas Gevaert
Institution:1. Department of Urology, University Hospitals Leuven, Leuven, Belgium;2. Department of Urology, AZ Klina, Brasschaat, Belgium;3. Department of Urology, AZ Klina, Brasschaat, Belgium

Contribution: ​Investigation (equal), Writing - review & editing (supporting);4. Department of Pathology, University Hospital Erlangen, Erlangen, Germany;5. Department of Pathology, Curie Institute, Paris, France;6. Department of Pathology, AZ Groeninge, Kortrijk, Belgium;7. Organ Systems, KU Leuven, Leuven, Belgium

Abstract:Cytokeratin 5 is a marker of basal molecular subtypes of muscle-invasive bladder cancer (MIBC), which correlates with worse overall survival compared to luminal subtypes. Our observations have not confirmed CK5 as a marker of high-grade (HG) disease in Ta non-muscle-invasive bladder cancer (NMIBC). Therefore, to understand the basal-luminal immunohistochemistry profile in Ta NMIBC, we performed immunohistochemistry for CK5, P40, P63 (basal), GATA3 and CK20 (luminal) and studied the correlation with HG and clinical outcome in 109 patients with Ta NMIBC. HG and low-grade (LG) diseases were scored in each patient. Four different CK5 patterns were evaluated: absent (median 41.3%), normal (72.5%), rising (84.4%) and full thickness (23.9%). The median percentage of GATA3 was 100%. HG disease and CK5 expression and rising CK5 pattern had a significant inverse correlation, whereas HG disease and CK20 expression had a significant positive correlation. We also found a significant inverse correlation between CK5 expression and CK20 expression. Quantitative PCR confirmed that the presence of CK5 correlated with up-regulation of CK5 RNA. None of the markers could differentiate patients with regard to clinical outcome. Our results suggest a role for CK5 and CK20 in differentiating between LG and HG disease in Ta NMIBC.
Keywords:basal  CK20  CK5  GATA3  immunohistochemistry  luminal  non-muscle-invasive bladder cancer
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