DNA repair-redox enzyme apurinic endonuclease in cervical cancer: evaluation of redox control of HIF-1alpha and prognostic significance.

ABSTRACT

The multifunctional apurinic/apyrimidinic endonuclease (Ape1/ref-1) plays a key role in the human DNA base excision repair pathway. Ape1/ref-1 has also been shown to be involved in the redox control of transactivation activities of hypoxia-inducible factor (HIF)-1alpha. The aim of our study was to investigate the expression of these proteins in early stage invasive cervical cancer. Expression of Ape1/ref-1 and HIF-1alpha was detected immunohistochemically in 88 samples of cervical cancer stage pT1b. The levels of the proteins were compared and the prognostic influence of Ape1/ref-1 expression was investigated. Strong nuclear expression of Ape1/ref-1 was observed in 9 cases (10.2%), moderate in 22 cases (25%), weak in 17 cases (19.3%), and absent in 40 cases (45.5%). Furthermore, no correlation between Ape1/ref-1 and HIF-1alpha expression was observed (p=0.864). We also found no relationship of Ape1/ref-1 expression and survival (p>0.05, log-rank test). From these studies, we have concluded that in cervical cancer there is no correlation between the upstream redox regulatory protein of HIF-1, i.e., Ape1/ref-1, and HIF-1alpha expression. However, these studies do not address any functional relationship between the two proteins.