Transcription factors Stat5a and Stat5b: Favorable prognostic markers in breast cancer

Abstract

22071 Background: We have previously reported that presence of nuclear localized, tyrosine phosphorylated Stat5 in breast carcinoma cells is associated with a highly favorable prognosis in a material of 209 patients with node-negative breast cancer. This initial analysis was performed on tissue array sections and not on whole sections. Furthermore, the initial study did not distinguish between Stat5a and Stat5b, since the phosphotyrosine-motif recognized by the antibody is the same in Stat5a and Stat5b. Stat5a and Stat5b are highly homologous transcription factors with overlapping but distinct regulation and biological effects. It has remained unclear whether both Stat5a and Stat5b contribute to the favorable prognosis associated with positive anti-phospho-Stat5 status. Methods: We have now performed a retrospective follow-up analysis of nuclear localized, tyrosine phosphorylated Stat5 in whole sections of breast cancer from an independent material of 400 node-negative breast cancer specimens with outcome data provided by the National Cancer Institute's Cooperative Breast Cancer Tissue Resource (CBCTR). We also analyzed levels of Stat5a and Stat5b individually and performed survival analyses. Results: Nuclear localized, tyrosine phosphorylated Stat5 remained a significant favorable prognostic marker in this independent follow-up material of human breast cancer, validating our previous data. Furthermore, nuclear localized Stat5a and Stat5b both correlated with favorable prognosis. In contrast, nuclear localized phosphorylated Stat3 did not significantly correlate with prognosis. Conclusions: Levels of nuclear localized, tyrosine phosphorylated Stat5a/b, alone or in conjunction with levels of nuclear Stat5a or Stat5b proteins, could be a cost-effective test identifying a subset of node-negative breast cancer patients with excellent prognosis who may be managed less aggressively following surgery. No significant financial relationships to disclose.