title: Prognostic and biological significance of peroxisome proliferator-activated receptor-gamma in luminal breast cancer.
abstract: Peroxisome proliferator-activated receptor-gamma (PPARγ) is an adopted orphan receptor that belongs to the nuclear receptor superfamily of transcription factors. PPARγ 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), PPARγ 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 PPARγ 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 PPARγ expression in BC series prepared as tissue microarrays (TMAs). PPARγ antibody specificity was confirmed using Western blotting. PPARγ 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). PPARγ 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 PPARγ levels. Survival analysis showed that PPARγ is associated with better outcome in the whole series as well as in luminal ER-positive class. Cox regression model showed that PPARγ is an independent predictor of outcome. Higher PPARγ was associated with longer survival in patients with ER-positive tumours who did not receive hormone therapy. PPARγ is a good prognostic marker associated with hormone receptors. In patients with luminal BCs, PPARγ is a marker of better prognosis and is associated with longer survival.
authors: Division of Cancer and Stem Cells, School of Medicine, University Of Nottingham, City Hosital Campus, Nottingham, NG5 1PB, UK, razvanfa@yahoo.co.uk.
authors: Rezvan
authors: R
authors: Abduljabbar
authors: Methaq Mueen
authors: MM
authors: Al-Kaabi
authors: Ola H
authors: OH
authors: Negm
authors: Dena
authors: D
authors: Jerjees
authors: Abir A
authors: AA
authors: Muftah
authors: Abhik
authors: A
authors: Mukherjee
authors: Chun F
authors: CF
authors: Lai
authors: Laki
authors: L
authors: Buluwela
authors: Simak
authors: S
authors: Ali
authors: Patrick J
authors: PJ
authors: Tighe
authors: Andrew
authors: A
authors: Green
authors: Ian
authors: I
authors: Ellis
authors: Emad
authors: E
authors: Rakha
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D047495:PPAR gamma / Q000378:metabolism*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D047495:PPAR gamma; D011960:Receptors, Estrogen