TOP2A as marker of response to pegylated lyposomal doxorubicin (PLD) in epithelial ovarian cancers

Abstract

ObjectiveRelapsed epithelial ovarian cancer (EOC) is frequently treated with pegylated liposomal doxorubicin (PLD). Unfortunately, most patients do not benefit from treatment. Prediction of response is crucial to optimize PLD use and avoid unnecessary toxicities. We aimed at assessing the value of topoisomerase II alpha (TOP2A) expression as predictive marker of response to PLD-based therapy in patients with relapsed EOCs.MethodsWe retrospectively analyzed Formalin Fixed Paraffin Embedded (FFPE) tissues from 101 patients with platinum resistant (PR) or partially platinum-sensitive (PPS) EOCs treated with PLD-based chemotherapy beyond second line in three referral cancer centers between January 2010 and June 2018. TOP2A expression was measured by immunohistochemistry (IHC): images of each sample were acquired by optical microscope and analyzed by using automatic counter software. Correlation between TOP2A expression and response to PLD was assessed. Since no cut-off for positivity has been validated yet, we dichotomized TOP2A expression based on a cut-off of 18% (mean value in this study).ResultsTOP2A expression beyond cut-off was not prognostic for primary platinum-free interval in our series (p = 0.77) neither for optimal cytoreduction (p = 0.9). TOP2A > 18% was associated with a longer time to progression (TTP) following PLD-treatment, although not statistically significant (p = 0.394). No difference was observed between PR and PPS patients’ groups (p = 0.445 and p = 0.185, respectively). Not unexpectedly, patients with TOP2A expression > 18% treated with PLD monotherapy achieved a longer TTP compared with PLD-doublet therapy (p = 0.05).ConclusionsOur data suggest that TOP2A status might predict activity of PLD in patients with PR/PPS EOCs.

Identification of potential hub genes associated with the pathogenesis and prognosis of hepatocellular carcinoma via integrated bioinformatics analysis

“…Topoisomerase II alpha (TOP2A), a potential biomarker for cancer therapy, has been detected in various types of cancer. 80 – 82 It participates in chromosome condensation and chromatid separation. 80 TOP2A encodes topoisomerase II alpha 81 and is reported to be overexpressed in HCC tissues.…”

“… 80 – 82 It participates in chromosome condensation and chromatid separation. 80 TOP2A encodes topoisomerase II alpha 81 and is reported to be overexpressed in HCC tissues. 83 Furthermore, a study has shown that TOP2A has prognostic value in HCC and its reactive agents can be used in HCC therapy.…”

Genomic heterogeneity in peritoneal implants: A differential analysis of gene expression using nanostring Human Cancer Reference panel identifies a malignant signature

“…Finally, TOPA2 encodes a DNA topoisomerase, an enzyme which releases torsional tension of the DNA duplex during transcription and replication [30]. A recent study shows that patients' tumors overexpressing TOPA2 might be more responsive to pegylated liposomal doxorubicin in platinum resistant ovarian cancer [31].…”

Human Ovarian Granulosa Cells Isolated during an IVF Procedure Exhibit Differential Expression of Genes Regulating Cell Division and Mitotic Spindle Formation

“…The enzyme encoded by this gene coordinates chromosomal condensation processes and chromatid formation and relieves any mechanical strains occurring during transcription and DNA replication. TOP2A can play an important prognostic role in epithelial ovarian cancer (EOC) [38]. It has also been indicated that TOP2A overexpression occurs in ovarian tumors: it is currently the main target of clinical trials of ovarian cancer therapies [39].…”