The association between the p53/topoisomerase I and p53/ topoisomerase IIalpha immunophenotypes and the progression of ovarian carcinomas.

BACKGROUND: In in vitro studies it has been revealed that p53 protein expression might regulate topoisomerase I (topo I) and topoisomerase IIalpha (topo IIalpha) levels in tumor cells. So far, the association between the p53 protein and topo I and topo IIalpha expression and its impact on ovarian carcinoma progression has not been analyzed.

OBJECTIVES: The aim of the study was to examine the association between topo I and topo IIalpha expression and p53 protein overexpression with respect to the morphological features and progressive growth of ovarian tumors.

MATERIAL AND METHODS: The expression of the studied biomarkers was estimated by immunohistochemical staining in tumor sections from 136 malignant and 30 benign ovarian neoplasms.

RESULTS: Significant differences for topo I, topo IIalpha and p53 expression between malignant and benign tumors were observed (p < 0.01). The expression of topo IIalpha and p53 protein was associated with advanced stages of ovarian carcinomas (p < 0.01). Differences between topo I-positive cases and low (G1) and high (G3) tumor grade had only borderline significance (p = 0.07). In ovarian carcinomas, positive correlations between topo I and topo IIalpha, topo I and p53 and topo Ilalpha and p53 protein expression were revealed (p = 0.001). No relationship between the studied biomarkers was found in benign ovarian tumors (p > 0.05). p53/topo I and p53/topo IIalpha immunophenotypes were associated with advanced stages of ovarian carcinoma (p = 0.045 and p = 0.009, respectively), p53/topo IIalpha positive ovarian carcinomas were more frequently observed in high than in low tumor grades and the differences were only of borderline significance (p = 0.07).

CONCLUSIONS: Current findings suggest that on the one hand, cooperation between topo I, topo IIalpha and p53 protein participates in the progressive growth of ovarian tumors. On the other hand, simultaneous expression of the studied proteins identifies the subgroup of ovarian cancers with aggressive biological features which might be considered in therapy.