Evaluation of TOP2A as a Predictive Marker for Endometrial Cancer With Taxane-Containing Adjuvant Chemotherapy

Int J Gynecol Cancer. 2016 Feb;26(2):325-30. doi: 10.1097/IGC.0000000000000607.

Abstract

Objective: Paclitaxel plus carboplatin and doxorubicin plus cisplatin are usually selected as adjuvant chemotherapy for endometrial cancer. However, biomarkers that can determine the appropriate chemotherapy regimen are not known. In the present study, we performed a retrospective investigation of the association between TOP2A, HER2 overexpression, and disease-free and overall survival in patients with endometrial cancer receiving taxane and platinum.

Methods: Eligible patients had a diagnosis of endometrial cancer based on histology and treated with an adjuvant chemotherapy regimen comprising taxane-platinum after surgery, and the HER2 and TOP2A status of the endometrial cancer regions was determined. Overall survival and disease-free survival between HER2 status and TOP2A status were estimated by the Kaplan-Meier method and compared using the log-rank test.

Results: We identified 56 patients who fulfilled the previously described criteria. Median follow-up was 49 months (range, 18-110 months). HER2-positive tumors were detected in 11 patients (19.6%), and TOP2A-positive tumors were detected in 7 patients (12.5%). Overall survival was not significantly different between patients with HER2-positive tumors and those with HER2-negative tumors, although disease-free survival for patients with HER2-positive tumors was significantly lower than disease-free survival for patients with HER2-negative tumors (P = 0.049). In contrast, patients with TOP2A-positive tumors had significantly lower overall survival than did patients with TOP2A-negative tumors (P = 0.020), and disease-free survival for patients with TOP2A-positive tumors tended to be shorter than for those with TOP2A-negative tumors.

Conclusions: Patients with TOP2A overexpression have a worse prognosis compared with those with TOP2A nonexpression, and TOP2A may be a useful biomarker in patients receiving adjuvant taxane-platinum regimens with moderate- to high-risk endometrial cancer.

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / metabolism*
  • Antineoplastic Agents / therapeutic use
  • Carboplatin / therapeutic use
  • Carcinoma, Endometrioid / drug therapy
  • Carcinoma, Endometrioid / metabolism*
  • Carcinoma, Endometrioid / mortality
  • Chemotherapy, Adjuvant
  • DNA Topoisomerases, Type II / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / mortality
  • Female
  • Humans
  • Middle Aged
  • Paclitaxel / therapeutic use
  • Poly-ADP-Ribose Binding Proteins
  • Receptor, ErbB-2 / metabolism*
  • Retrospective Studies

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Poly-ADP-Ribose Binding Proteins
  • Carboplatin
  • Receptor, ErbB-2
  • DNA Topoisomerases, Type II
  • TOP2A protein, human
  • Paclitaxel