Universität zu Köln

Roedel, Franz, Martin, Daniel ORCID: 0000-0002-8674-2683, Helmke, Christina, Balermpas, Panagiotis ORCID: 0000-0001-5261-6446, Fokas, Emmanouil, Wieland, Ulrike, Rave-Fraenk, Margret, Kitz, Julia, Matthess, Yves, Raab, Monika, Strebhardt, Klaus ORCID: 0000-0003-2173-9763 and Roedel, Claus (2016). 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. Oncotarget, 7 (33). S. 53339 - 53350. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

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/p16(INK4a) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Roedel, Franz UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin, Daniel UNSPECIFIED orcid.org/0000-0002-8674-2683 UNSPECIFIED Helmke, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Balermpas, Panagiotis UNSPECIFIED orcid.org/0000-0001-5261-6446 UNSPECIFIED Fokas, Emmanouil UNSPECIFIED UNSPECIFIED UNSPECIFIED Wieland, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Rave-Fraenk, Margret UNSPECIFIED UNSPECIFIED UNSPECIFIED Kitz, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Matthess, Yves UNSPECIFIED UNSPECIFIED UNSPECIFIED Raab, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Strebhardt, Klaus UNSPECIFIED orcid.org/0000-0003-2173-9763 UNSPECIFIED Roedel, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-266486
DOI:	10.18632/oncotarget.10801
Journal or Publication Title:	Oncotarget
Volume:	7
Number:	33
Page Range:	S. 53339 - 53350
Date:	2016
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS ONCOPROTEINS; NECK-CANCER; INFILTRATING LYMPHOCYTES; SERINE/THREONINE KINASE; OROPHARYNGEAL CANCER; RADIATION RESPONSE; RECTAL-CANCER; EXPRESSION; HPV Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26648