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

Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is an adopted orphan receptor that belongs to the nuclear receptor superfamily of transcription factors. PPAR gamma 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 gamma 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 gamma 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 gamma expression in BC series prepared as tissue microarrays (TMAs). PPAR gamma antibody specificity was confirmed using Western blotting. PPAR gamma 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 gamma 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 gamma levels. Survival analysis showed that PPAR gamma is associated with better outcome in the whole series as well as in luminal ER-positive class. Cox regression model showed that PPAR gamma is an independent predictor of outcome. Higher PPAR gamma was associated with longer survival in patients with ER-positive tumours who did not receive hormone therapy. PPAR gamma is a good prognostic marker associated with hormone receptors. In patients with luminal BCs, PPAR gamma is a marker of better prognosis and is associated with longer survival.