DNA topoisomerase II-alpha immunoreactivity as a marker of tumor aggressiveness in invasive breast cancer

Objective: The nuclear enzyme DNA topoisomerase (topo) II breaks and rejoin s DNA strands; its isoform topo II alpha is associated with active cell pro liferation of mammalian cells. The aim of this study was to examine the rel ationship between the expression of topo II alpha and biological behavior m arkers in breast cancer. Methods: Formalin-fixed, paraffin-embedded tissue from 88 samples of infiltrating breast cancer was immunohistochemically sta ined for topo II alpha. For each case, a topo II alpha index was determined by image analysis. Similar indexes were available for Ki-67 protein, a kno wn cell proliferation marker, and p53, bcl-2 and c-erbB-2 oncoproteins. Eac h case had been staged and graded and the patients had been followed up for a mean period of 61.62 months. Results: Elevated topo II alpha immunoposit ivity (in >10% of malignant nuclei) was detected in 22 tumors, and this imm unostatus was statistically associated with poor nuclear differentiation, a bsence of steroid hormone receptors, high Ki-67 immunoexpression, p53 prote in accumulation and c-erbB-2 protein overexpression. Topo II alpha expressi on was not linked with disease extent (stage or lymph node status). Neither proliferation marker (topo II alpha or Ki-67) had any significant influenc e on the patients' recurrence-free survival. Conclusion: From the above res ults, we conclude that topo II alpha overexpression appears to be linked wi th cellular dedifferentiation and potentially aggressive tumor phenotype in invasive breast cancer. Copyright (C) 2001 S. Karger AG, Basel.