Prognostic role of topoisomerase-IIalpha in advanced ovarian cancer patients

Abstract

To our knowledge, very few data about the role of Topoisomerase IIalpha (TOPO-IIalpha), 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-IIalpha 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-IIalpha antibody (clone Ki-S1). TOPO-IIalpha 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 (chi(2)=6.6, P-value=0.0101). In multivariate analysis, only platinum resistance, advanced stage of disease and high levels of TOPO-IIalpha expression retained an independent negative prognostic role for OS. The unfavourable role of high TOPO-IIalpha expression was maintained only in the subgroup of platinum resistant recurrent ovarian cancer patients, be TOPO-IIalpha expression evaluated as continuous variable (chi(2)=5.1, P-value=0.024), or by means of the defined cutoff point. Our study suggests that the assessment of TOPO-IIalpha could be helpful to identify poor prognosis platinum-resistant ovarian cancer patients, potentially candidates to investigational agents.

Figure 1

TOPO-IIα immunoreaction in primary ovarian cancer. (A) Positive control (human breast cancer tissue specimen), (B) negative control (ovarian carcinoma) for TOPO-IIα staining. Representative examples of high (C) and low (D) TOPO-IIα expression. (A, B, C, D) Magnification= × 200.

Figure 2

Plot of the estimates of the relative risk of progression (A) and death (B) of disease as a prediction of TOPO-IIα values, calculated by COX's proportional hazard regression model.

Figure 3

Overall survival curves in ovarian cancer patients according to the status of TOPO-IIα.