Prognostic and biological significance of peroxisome proliferator-activated receptor-gamma in luminal breast cancer

Peroxisome proliferator-activated receptor-gamma (PPAR γ ) is an adopted orphan receptor that belongs to the nuclear receptor superfamily of transcription factors. PPAR γ is regarded as a differentiation factor and it plays an important role in regulating adipogenesis, cell growth, proliferation and tumour progression. In breast cancer (BC), PPAR γ agonists were reported to inhibit proliferation and growth invasion and promote phenotypic changes associated with a less malignant and more differentiated status. This study aims to assess the prognostic and biological roles of PPAR γ protein expression in a large cohort of BC patients ( n = 1100) with emphasis on the luminal oestrogen receptor (ER) positive class. Immunohistochemistry was used to assess the levels of PPAR γ expression in BC series prepared as tissue microarrays (TMAs). PPAR γ antibody specificity was confirmed using Western blotting. PPAR γ nuclear expression was detected in 79 % of the cases and its expression was positively correlated with the hormonal receptors (ER, progesterone receptor and androgen receptor). PPAR γ levels were significantly higher in tumours with lobular subtype, smaller size and lower grade, while HER2-positive, ductal or medullary tumours were associated with lower PPAR γ levels. Survival analysis showed that PPAR γ is associated with better outcome in the whole series as well as in luminal ER-positive class. Cox regression model showed that PPAR γ is an independent predictor of outcome. Higher PPAR γ was associated with longer survival in patients with ER-positive tumours who did not receive hormone therapy. PPAR γ is a good prognostic marker associated with hormone receptors. In patients with luminal BCs, PPAR γ is a marker of better prognosis and is associated with longer survival.