Nuclear staining of FGFR-2/ STAT-5 and RUNX-2 in mucinous breast cancer: role for FGF pathway

Abstract

Background Mucinous carcinomas account for 2% of breast cancers, and display a distinctive gene expression prole. We reported that FGF-2 activates progesterone receptors (PRs) and STAT-5 through FGFR-2 in T47D cells. It is known that FGF-2 or STAT-5 also activates RUNX-2. We found a strong correlation between the nuclear expression of FGFR-2 and STAT-5 or RUNX-2. The aim was to increase the number of mucinous cases to evaluate the expression of FGFR-2, STAT-5 and RUNX-2. Methods Fifty paraffin embedded breast carcinoma samples expressing ERct and PR were selected: 43 belong to IDC-NSTs and 7 to mucinous subtype. Samples were analyzed by IHC for ER, PR, FGFR2, STAT5 and RUNX2. Results In the IDC group the results: were: FGFR-2 74.4% (32/43), STAT-5 48.8% (21/43), RUNX-2 22.8% (8/43) of nuclear expression when evaluating each protein independently. Only 18.6% of the samples co-expressed the 3 proteins in the nucleus. Conversely, mucinous subtype 86% ( p 0.01) showed nuclear co-expression. Conclusion Nuclear co-expression of STAT-5, RUNX-2 and FGFR-2 may be part of the signature for mucinous subtype. Our data show a similar nuclear FGFR-2 and STAT5 localization as T47D cells stimulated by FGF2, suggesting that mucin may provide fibroblast growth factors activating PR.