Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis.
<h4>Purpose</h4>Genome-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.<h4>Materials and methods</h4>Tumor samples from 222 patients with upper...
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| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0179602&type=printable |
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| author | Danijel Sikic Bastian Keck Sven Wach Helge Taubert Bernd Wullich Peter J Goebell Andreas Kahlmeyer Peter Olbert Philipp Isfort Wilhelm Nimphius Arndt Hartmann Johannes Giedl Bridge Consortium |
| author_facet | Danijel Sikic Bastian Keck Sven Wach Helge Taubert Bernd Wullich Peter J Goebell Andreas Kahlmeyer Peter Olbert Philipp Isfort Wilhelm Nimphius Arndt Hartmann Johannes Giedl Bridge Consortium |
| author_sort | Danijel Sikic |
| collection | DOAJ |
| description | <h4>Purpose</h4>Genome-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.<h4>Materials and methods</h4>Tumor 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).<h4>Results</h4>Hierarchical 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.<h4>Conclusions</h4>Immunohistochemical 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. |
| first_indexed | 2024-12-11T10:06:46Z |
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| id | doaj.art-591a4179080042ae9e9bad876a1ca95a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-14T14:07:22Z |
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| spelling | doaj.art-591a4179080042ae9e9bad876a1ca95a2025-02-27T05:38:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01126e017960210.1371/journal.pone.0179602Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis.Danijel SikicBastian KeckSven WachHelge TaubertBernd WullichPeter J GoebellAndreas KahlmeyerPeter OlbertPhilipp IsfortWilhelm NimphiusArndt HartmannJohannes GiedlBridge Consortium<h4>Purpose</h4>Genome-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.<h4>Materials and methods</h4>Tumor 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).<h4>Results</h4>Hierarchical 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.<h4>Conclusions</h4>Immunohistochemical 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0179602&type=printable |
| spellingShingle | Danijel Sikic Bastian Keck Sven Wach Helge Taubert Bernd Wullich Peter J Goebell Andreas Kahlmeyer Peter Olbert Philipp Isfort Wilhelm Nimphius Arndt Hartmann Johannes Giedl Bridge Consortium Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis. PLoS ONE |
| title | Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis. |
| title_full | Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis. |
| title_fullStr | Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis. |
| title_full_unstemmed | Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis. |
| title_short | Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis. |
| title_sort | immunohistochemiocal subtyping using ck20 and ck5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0179602&type=printable |
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