P2.27 DNA Polymerase ζ as a Prognostic Biomarker for Cervical Carcinoma

Abstract

ABSTRACT Objective DNA Polymerase ζ (Polζ), an error-prone DNA polymerase involved in translesion DNA synthesis, plays a significant role in the cytotoxicity, mutagenicity, and chemoresistance of several cancers. The association of Polζ with chemoradiation resistance and prognosis of cervical cancer patients needs exploration. Methods One hundred and twenty three patients with squamous cell carcinoma of cervical cancer (CSCC) who had adjuvant concurrent chemoradiation therapy after radical surgery treated at Fudan University Shanghai Cancer Center between 2008 and 2009 were enrolled in this study. We tested their in vitro platinum resistance using the MTT method and the expression of Polζ in paraffin-embedded tissue samples using immunohistochemistry. Results Expression of Polζ was detected in 22 % (25/116) of the specimens. The median in vitro inhibition rate of tumor cell growth by cisplatin, carboplatin, nedaplatin and oxaliplatin was 80 %, 37 %, 78 % and 51 %, respectively. Among the tumor-related variables, FIGO stage (adjusted HR 6·7, 95 % CI 1·7-26·4, P = 0·007) and the Polζ protein expression (adjusted HR 6·5, 95 % CI 1·7-25·0, P = 0·006) were found to be significant predictors of progression-free survival (PFS) for the multivariate analysis. Kaplan-Meier survival estimates showed that the patients with high stage and Polζ-positive expression had a significantly shorter PFS. However, the association between Polζ expression and in vitro platinum-inhibition rates was not significant. Conclusion Polζ expression can be used as the predictor for poor prognosis, which might be caused by the potential chemoradiation resistance of the patients. The mechanism deserves further exploration.