ArticlePloS one2017
Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- The Diagnostic and Prognostic Value of Immunohistochemical Markers in Bladder Cancer: A Real-World Study of 477 Patients.Journal of clinical medicine · 2026Article
- AIF, CK5/6, and CK20 in Bladder Urothelial Carcinoma: A Cross-Sectional Immunohistochemical Study of Grade and Stage Associations.Journal of clinical medicine · 2026Article
- Immunohistochemistry-based risk stratification of upper tract urothelial carcinoma.Frontiers in oncology · 2026Article
- Human epidermal growth factor receptor 2 overexpression is associated with high-grade tumors in upper tract urothelial carcinoma.World journal of clinical oncology · 2025Article
- The Role of Immunohistochemistry as a Surrogate Marker in Molecular Subtyping and Classification of Bladder Cancer.Diagnostics (Basel, Switzerland) · 2024Review
- Biomarker Profiling of Upper Tract Urothelial Carcinoma Only and with Synchronous or Metachronous Bladder Cancer.Biomedicines · 2024Article
- A deep-learning workflow to predict upper tract urothelial carcinoma protein-based subtypes from H&E slides supporting the prioritization of patients for molecular testing.The journal of pathology. Clinical research · 2024Article
- Complete remission following pembrolizumab therapy for a patient with nephroureterectomy positive-margin carcinoma in situ and bladder cancer unresponsive to Bacille Calmette-Guérin therapy.SAGE open medical case reports · 2023Article
- Are We Ready to Implement Molecular Subtyping of Bladder Cancer in Clinical Practice? Part 2: Subtypes and Divergent Differentiation.International journal of molecular sciences · 2022Review
- Are We Ready to Implement Molecular Subtyping of Bladder Cancer in Clinical Practice? Part 1: General Issues and Marker Expression.International journal of molecular sciences · 2022Review
- Cytokeratin 5 and cytokeratin 6 expressions are unconnected in normal and cancerous tissues and have separate diagnostic implications.Virchows Archiv : an international journal of pathology · 2022Article
- Construction and Verification of Immunohistochemistry Parameters-Based Classifier to Predict Local-Recurrence of Upper Tract Urothelial Carcinoma After Kidney-Sparing Surgery.Frontiers in oncology · 2022Article
- Cytokeratin 5 and cytokeratin 20 inversely correlate with tumour grading in Ta non-muscle-invasive bladder cancer.Journal of cellular and molecular medicine · 2021Article
- Intratumoral heterogeneity of surrogate molecular subtypes in urothelial carcinoma in situ of the urinary bladder: implications for prognostic stratification of high-risk non-muscle-invasive bladder cancer.Virchows Archiv : an international journal of pathology · 2021Article
- Factors Predicting Oncological Outcomes of Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma in Taiwan.Frontiers in oncology · 2021Article
- Combined use of immunohistochemical markers of basal and luminal subtypes in urothelial carcinoma of the bladder: Association with clinicopathological features and outcomes.Clinics (Sao Paulo, Brazil) · 2021Article
- CK20 and CK5/6 Immunohistochemical Staining of Urothelial Neoplasms: A Perspective.Advances in urology · 2020Review
- Patterns and risks of postoperative recurrence in completely resected EGFR-mutant non-small cell lung cancer: prognostic significance of routine immunohistochemical markers.Translational lung cancer research · 2019Article
- Predicting outcomes in non-muscle invasive (Ta/T1) bladder cancer: the role of molecular grade based on luminal/basal phenotype.Virchows Archiv : an international journal of pathology · 2019Article
- Transcriptional Analysis of Immunohistochemically Defined Subgroups of Non-Muscle-Invasive Papillary High-Grade Upper Tract Urothelial Carcinoma.International journal of molecular sciences · 2019Article
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeGenome-wide analyses revealed basal and luminal subtypes of urothelial carcinomas of the bladder. It is unknown if this subtyping can also be applied to upper tract urothelial carcinomas. MATERIALS AND
methodsTumor samples from 222 patients with upper tract urothelial carcinomas who were treated with radical nephroureterectomy were analyzed for the expression of seven basal/luminal immunohistochemical markers (CK5, EGFR, CD44, CK20, p63, GATA3, FOXA1).
resultsHierarchical clustering revealed a basal-like subtype (enrichment of CK5, EGFR and CD44) in 23.9% and a luminal-like subtype (enrichment of CK20, GATA3, p63 and FOXA1) in 13.1% of the patients. In 60.8%, little to no markers were expressed, whereas markers of both subtypes were expressed in 2.2%. By using CK5 and CK20 as surrogate markers for the basal and luminal subtypes, we defined four subtypes of upper tract urothelial carcinomas: (i) exclusively CK20 positive and CK5 negative (CK20+/CK5-), (ii) exclusively CK5 positive and CK20 negative (CK20-/ CK5+), (iii) both markers positive (CK20+/CK5+) and (iv) both markers negative (CK20-/CK5-). A receiver-operator analysis provided the optimal cut-off values for this discrimination. An immunoreactive score >1 for CK5 and >6 for CK20 were defined as positive. In multivariate Cox's regression analysis, the CK20+/CK5- subtype was an independent negative prognostic marker with a 3.83-fold increased risk of cancer-specific death (p = 0.02) compared to the other three subtypes.
conclusionsImmunohistochemical subgrouping of upper tract urothelial carcinomas by analyzing CK5 and CK20 expression can be performed in a routine setting and can identify tumors with a significantly worse cancer-specific survival prognosis.
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