Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis
Sikic D, Keck B, Wach S, Taubert H, Wullich B, Goebell P, Kahlmeyer A, Olbert P, Isfort P, Nimphius W, Hartmann A, Giedl J (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 12
Pages Range: e0179602
Journal Issue: 6
DOI: 10.1371/journal.pone.0179602
Abstract
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.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).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.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.
Authors with CRIS profile
Bastian Keck
Medizinische Fakultät
Helge Taubert
Urologische Klinik
Bernd Wullich
Lehrstuhl für Urologie
Peter Goebell
Urologische Klinik
Arndt Hartmann
Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie
Involved external institutions
Germany (DE)How to cite
APA:
Sikic, D., Keck, B., Wach, S., Taubert, H., Wullich, B., Goebell, P.,... Giedl, J. (2017). Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis. PLoS ONE, 12(6), e0179602. https://dx.doi.org/10.1371/journal.pone.0179602
MLA:
Sikic, Danijel, et al. "Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis." PLoS ONE 12.6 (2017): e0179602.
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