Pathology & Oncology Research

, Volume 18, Issue 1, pp 61–68

Tumour Topoisomerase II Alpha Protein Expression and Outcome After Adjuvant Dose-Dense Anthracycline-Based Chemotherapy

  • Alíz Nikolényi
  • Gabriella Uhercsák
  • Melinda Csenki
  • Sándor Hamar
  • Erika Csörgő
  • Ervin Tánczos
  • László Thurzó
  • Thomas Brodowicz
  • Maria Wagnerova
  • Zsuzsanna Kahán
Research

DOI: 10.1007/s12253-011-9417-4

Cite this article as:
Nikolényi, A., Uhercsák, G., Csenki, M. et al. Pathol. Oncol. Res. (2012) 18: 61. doi:10.1007/s12253-011-9417-4

Abstract

There is a need for the selection of those breast cancers where benefit may be attained from the addition of an anthracycline to the adjuvant chemotherapy. The expression of topoisomerase II alpha (TOP2A) protein in 3 cohorts of breast cancers treated with adjuvant dose-dense anthracycline-based chemotherapy was determined retrospectively. The TOP2A status was analysed in relation with the other standard tumour features and the outcome. TOP2A IHC results were assessable in 106 patients: with a cut-off value of 15%, 48% of the tumours were classified as TOP2A-positive. The expression of TOP2A correlated with that of Ki67 (R = 0.532, p < 0.001) and a high grade (p = 0.04), but did not correlate with the proportion of ER- or PR-positive cells in the tumour. More tumors were TOP2A-negative among the ER- or PR-positive cancers than among the ER/PR-negative cancers (p = 0.021 and p = 0.002, respectively). After a median follow-up time of 64.5 months, 31 relapses (23.5%) and 23 deaths (17.4%) had occurred in 131 patients. The overall survival was longer in the TOP2A-positive cases than in the TOP2A-negative cases. The recurrence-free survival and the overall survival were significantly more favourable in the ER/PR-negative and TOP2A-positive tumours than in other subgroups. In a Cox proportional hazards model, the grade and TOP2A remained significant determinants in the ER/PR-negative subgroup. TOP2A positivity and grade 3 indicated a decrease in the risk of death with HR = 0.211 (95% CI: 0.042–1.05, p = 0.056) and HR = 0.216 (95% CI: 0.047–0.990, p = 0.048), respectively. A higher sensitivity to anthracycline-containing regimens is suggested in ER/PR-negative and TOP2A-positive cancers.

Keywords

Anthracyclines Adjuvant chemotherapy Breast cancer Dose-dense chemotherapy Topoisomerase II alpha 

Abbreviations

A

adriamycin

ADC

adriamycin (A)-docetaxel (D)-cyclophosphamide (C) chemotherapy study

ATC

adriamycin (A)-paclitaxel (T)-cyclophosphamide (C) chemotherapy study

C

cyclophosphamide

CECOG

Central European Cooperative Oncology Group

D

docetaxel

ER

estrogen receptor

FEC

fluorouracil-epirubicin-cyclophosphamide chemotherapy

FISH

fluorescence in situ hybridisation

GCSF

granulocyte colony stimulating factor

IHC

immunohistochemistry

LVI

lymphovascular invasion

OS

overall survival

PR

progesterone receptor

RFS

recurrence-free survival

RNA

ribonucleic acid

T

paclitaxel

TOP2A

topoisomerase II alpha

Copyright information

© Arányi Lajos Foundation 2011

Authors and Affiliations

  • Alíz Nikolényi
    • 1
  • Gabriella Uhercsák
    • 1
  • Melinda Csenki
    • 1
  • Sándor Hamar
    • 2
  • Erika Csörgő
    • 2
  • Ervin Tánczos
    • 3
  • László Thurzó
    • 1
  • Thomas Brodowicz
    • 4
  • Maria Wagnerova
    • 5
  • Zsuzsanna Kahán
    • 1
  1. 1.Department of OncotherapyUniversity of SzegedSzegedHungary
  2. 2.Department of PathologyUniversity of SzegedSzegedHungary
  3. 3.Department of Medical InformaticsUniversity of SzegedSzegedHungary
  4. 4.Central European Cooperative Oncology GroupViennaAustria
  5. 5.Department of Radiotherapy and OncologyOncology InstituteKosiceSlovakia

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