Prognostic role of topoisomerase-IIα in advanced ovarian cancer patients

Abstract

To our knowledge, very few data about the role of Topoisomerase IIα (TOPO-IIα), an enzyme involved in critical steps of tumour cell proliferation and chemoresistance are currently available in ovarian cancer patients. The aim of this study was to investigate the prognostic value of TOPO-IIα expression in a large, single institution series of 96 primary untreated advanced ovarian cancer patients admitted to the Gynecologic Oncology Unit, Catholic University of Campobasso and Rome. Immunohistochemistry was carried out by using the MoAb anti-human TOPO-IIα antibody (clone Ki-S1). TOPO-IIα immunoreaction was observed in 70 out of 96 cases (72.9%), and the percentages of positively stained cells ranged between 1 and 83% (median=10%). There was no association with clinico-pathological parameters. During the follow up period, progression and death of disease were observed in 76 (79.2%) and 45 (46.9%) cases. A statistically significant direct association between the percentages of positively immunostained tumour cells and the relative risk of death was observed (χ²=6.6, P-value=0.0101). In multivariate analysis, only platinum resistance, advanced stage of disease and high levels of TOPO-IIα expression retained an independent negative prognostic role for OS. The unfavourable role of high TOPO-IIα expression was maintained only in the subgroup of platinum resistant recurrent ovarian cancer patients, be TOPO-IIα expression evaluated as continuous variable (χ²=5.1, P-value=0.024), or by means of the defined cutoff point. Our study suggests that the assessment of TOPO-IIα could be helpful to identify poor prognosis platinum-resistant ovarian cancer patients, potentially candidates to investigational agents.