TY  - JOUR
A1  - Rödel, Franz
A1  - Martin, Daniel
A1  - Helmke, Christina
A1  - Balermpas, Panagiotis
A1  - Fokas, Emmanouil
A1  - Wieland, Ulrike
A1  - Rave-Fränk, Margret
A1  - Kitz, Julia
A1  - Matthess, Yves
A1  - Raab, Monika
A1  - Strebhardt, Klaus
A1  - Rödel, Claus
T1  - 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
T2  - OncoTarget
N2  - 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.
KW  - anal carcinoma
KW  - Polo-like kinase 3
KW  - caspase-8
KW  - chemoradiotherapy
KW  - local control
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45625
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-456252
SN  - 1949-2553
N1  - All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
VL  - 7
IS  - 33
SP  - 53339
EP  - 53349
PB  - Impact Journals LLC
CY  - [s. l.]
ER  -