Study of the topographic distribution of ets-1 protein expression in invasive breast carcinomas in relation to tumor phenotype.

BACKGROUND

Ets-1 is a transcription factor, implicated in the regulation of expression of various genes'. The aim of the present study was to investigate the expression of ets-1 protein in invasive breast carcinomas and its correlation with classic clinicopathological parameters, patients' survival and various biological markers.

METHODS

Immunohistochemistry was performed in paraffin-embedded tissue specimens from 149 invasive breast carcinomas to detect the proteins ets-1, p53, topoisomerase IIalpha, matrix metalloproteinase-7 (MMP-7) and urokinase-type plasminogen activator receptor (uPAR). Results were subjected to univariate and multivariate statistic analysis.

RESULTS

Ets-1 protein was detected in the 77.9% of the cases in the cytoplasm, in the 46.3% in the nucleus of the malignant cells, and in stromal fibroblasts as well. Cytoplasmic ets-1 was inversely correlated with nuclear and histologic grade of the tumor (p=0.004 and 0.033, respectively) and topoisomerase IIotaalpha (p=0.057), while nuclear ets-1 showed a positive association with p53 (p=0.002). Stromal ets-1 revealed a negative correlation with estrogen receptors (ER) (p=0.003) and a positive one with stromal uPAR and MMP-7 as well (p=0.048 and 0.066, respectively). The univariate statistic analysis showed nuclear ets-1 to be related to a shortened overall survival of the postmenopausal patients (p=0.032).

CONCLUSIONS

Ets-1 seems to be related to a different tumor phenotype according to its topographic distribution, with nuclear localization being associated with decreased apoptotic potential of the malignant cells through its relation to the mutant p53 protein, cytoplasmic being related to a favorable tumor phenotype and stromal ets-1 being related to tumor invasion.