Prognostic role of topoisomerase-IIα in advanced ovarian cancer patients

Abstract

To our knowledge, very few data about the role of Topoisomerase IIa (TOPO-IIa), 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-IIa 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-IIa antibody (clone Ki-S1). TOPO-IIa immunoreaction was observed in 70 out of 96 cases (72.9%), and the percentages of positively stained cells ranged between 1 and 83% (median ¼ 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 (w 2 ¼ 6.6, P-value ¼ 0.0101). In multivariate analysis, only platinum resistance, advanced stage of disease and high levels of TOPO-IIa expression retained an independent negative prognostic role for OS. The unfavourable role of high TOPO-IIa expression was maintained only in the subgroup of platinum resistant recurrent ovarian cancer patients, be TOPO-IIa expression evaluated as continuous variable (w 2 ¼ 5.1, P-value ¼ 0.024), or by means of the defined cutoff point. Our study suggests that the assessment of TOPO-IIa could be helpful to identify poor prognosis platinum-resistant ovarian cancer patients, potentially candidates to investigational agents.

Clinical significance of topoisomerase‐II expression in patients with advanced non‐small cell lung cancer treated with amrubicin

“…We found that high Topo‐II expression was an independent factor for reduced OS in patients with advanced NSCLC receiving amrubicin. Consistent with our observation, high Topo‐II expression has previously been shown to be significantly related to reduced OS in various cancers including urinary bladder carcinoma, breast cancer, gallbladder carcinoma, ovarian cancer, hepatocellular carcinoma, Hodgkin's lymphoma and prostate cancer . In an in vitro study, the expression levels of Topo‐IIα were found to be closely related to tumor cell proliferation and aggression .…”

Targeting of topoisomerases for prognosis and drug resistance in ovarian cancer

“…So far, numerous studies had mainly focused on TOP2A. Elevated TOP2A mRNA were observed in high grade ovarian cancers as well as advanced stage diseases, and patients with overexpression of nuclear TOP2A protein had a marked decreased OS [ 44 – 46 ]. In our study, for all EOC patients and serous patients, the TOP2A overexpression was associated with significantly worse OS, but insignificantly better OS in endomitrioid patients, maybe due to tumor heterogeneity as well as the small and unbalanced sample sizes.…”

Expression of Topoisomerase II‑α protein in salivary gland tumors

“…(Topo II-α) has been extensively researched for its role as a molecular target of chemotherapy agents. Several studies have suggested that Topo II-α expression is related to response to anthracycline treatment for breast cancer (11)(12)(13), renal medullary carcinoma (14), ovarian carcinoma (15), salivary gland tumors (16,17), acute myeloid leukemia (18), Hodgkin's lymphoma (19), colorectal cancer (20), hepatocellular carcinoma (21), gallbladder carcinoma (22), prostate carcinoma (23), and other malignant tumors (24). Thus, these cancer types benefit from using Topo II-α as a prognostic marker, and also for individual tailored therapy.…”