Polo-like kinase 3 and phosphoT273 caspase-8 are associated with improved local tumor control and survival in patients with anal carcinoma treated with concomitant chemoradiotherapy

We have recently shown that caspase-8 is a new substrate of Polo-like kinase 3 (Plk3) that phosphorylates the protein on residue T273 thereby promoting its pro-apoptotic function. In the present study we aimed to investi
We have recently shown that caspase-8 is a new substrate of Polo-like kinase 3 (Plk3) that phosphorylates the protein on residue T273 thereby promoting its pro-apoptotic function. In the present study we aimed to investigate the clinical relevance of Plk3 expression and phosphorylation of caspase-8 at T273 in patients with anal squamous cell carcinoma (SSC) treated with 5-fluorouracil and mitomycin C-based chemoradiotherapy (CRT). Immunohistochemical detection of the markers was performed in pretreatment biopsy specimens of 95 patients and was correlated with clinical/histopathologic characteristics including HPV-16 virus load/p16INK4a expression and cumulative incidence of local and distant failure, cancer specific survival (CSS), and overall survival (OS). We observed significant positive correlations between Plk3 expression, pT273 caspase-8 signal, and levels of HPV-16 virus DNA load/p16INK4a detection. Patients with high scores of Plk3 and pT273 caspase-8 showed increased local control (p = 0.011; p = 0.001), increased CSS (p = 0.011; p = 0.013) and OS (p = 0.024; p = 0.001), while the levels of pT273 caspase-8 were significantly associated (p = 0.033) with distant metastases. In multivariate analyses Plk3 expression remained significant for local failure (p = 0.018), CSS (p = 0.016) and OS (p = 0.023). Moreover, a combined HPV16 DNA load and Plk3 or pT273 caspase-8 variable revealed a significant correlation to decreased local failure (p = 0.001; p = 0.009), increased CSS (p = 0.016; p = 0.023) and OS (p = 0.003; p = 0.003). In conclusion these data indicate that elevated levels of Plk3 and pT273 caspase-8 are correlated with favorable clinical outcome in patients with anal SCC treated with concomitant CRT.
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Metadaten
Author:Franz Rödel, Daniel Martin, Christina Helmke, Panagiotis Balermpas, Emmanouil Fokas, Ulrike Wieland, Margret Rave-Fränk, Julia Kitz, Yves Matthess, Monika Raab, Klaus Strebhardt, Claus Rödel
URN:urn:nbn:de:hebis:30:3-456252
DOI:http://dx.doi.org/10.18632/oncotarget.10801
ISSN:1949-2553
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=27462786
Parent Title (English):OncoTarget
Publisher:Impact Journals LLC
Place of publication:[s. l.]
Document Type:Article
Language:English
Year of Completion:2016
Date of first Publication:2016/07/23
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/02/06
Tag:Polo-like kinase 3; anal carcinoma; caspase-8; chemoradiotherapy; local control
Volume:7
Issue:33
Pagenumber:11
First Page:53339
Last Page:53349
Note:
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
HeBIS PPN:426623479
Institutes:Biowissenschaften
Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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