DNA Topoisomerase II-Alpha Immunoreactivity as a Marker of Tumor Aggressiveness in Invasive Breast Cancer

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Abstract
The nuclear enzyme DNA topoisomerase (topo) II breaks and rejoins DNA strands; its isoform topo IIalpha is associated with active cell proliferation of mammalian cells. The aim of this study was to examine the relationship between the expression of topo IIalpha and biological behavior markers in breast cancer. Formalin-fixed, paraffin-embedded tissue from 88 samples of infiltrating breast cancer was immunohistochemically stained for topo IIalpha. For each case, a topo IIalpha index was determined by image analysis. Similar indexes were available for Ki-67 protein, a known cell proliferation marker, and p53, bcl-2 and c-erbB-2 oncoproteins. Each case had been staged and graded and the patients had been followed up for a mean period of 61.62 months. Elevated topo IIalpha immunopositivity (in >10% of malignant nuclei) was detected in 22 tumors, and this immunostatus was statistically associated with poor nuclear differentiation, absence of steroid hormone receptors, high Ki-67 immunoexpression, p53 protein accumulation and c-erbB-2 protein overexpression. Topo IIalpha expression was not linked with disease extent (stage or lymph node status). Neither proliferation marker (topo IIalpha or Ki-67) had any significant influence on the patients' recurrence-free survival. From the above results, we conclude that topo IIalpha overexpression appears to be linked with cellular dedifferentiation and potentially aggressive tumor phenotype in invasive breast cancer.