An immunohistochemical perspective of PPARβ and one of its putative targets PDK1 in normal ovaries, benign and malignant ovarian tumours

Abstract

Peroxisome proliferator-activated receptor β (PPARβ) is a member of the nuclear hormone receptor family and is a ligand-activated transcription factor with few known molecular targets including 3-phosphoinositide-dependent protein kinase 1(PDK1). In view of the association of PPARβ and PDK1 with cancer, we have examined the expression of PPARβ and PDK1 in normal ovaries and different histological grades of ovarian tumours. Normal ovaries, benign, borderline, grades 1, 2 and 3 ovarian tumours of serous, muciuous, endometrioid, clear cell and mixed subtypes were analysed by immunohistochemistry for PPARβ and PDK1 expression. All normal ovarian tissues, benign, borderline and grade 1 tumours showed PPARβ staining localised in the epithelium and stroma. Staining was predominantly nuclear, but some degree of cytoplasmic staining was also evident. Approximately 20% of grades 2 and 3 tumours lacked PPARβ staining, whereas the rest displayed some degree of nuclear and cytoplasmic staining of the scattered epithelium and stroma. The extent of epithelial and stromal PPARβ staining was significantly different among the normal and the histological grades of tumours (χ²=59.25, d.f.=25, Pχ²=64.48, d.f.=25, Pβ was observed in the epithelium and stroma of benign and borderline tumours compared with grades 1, 2 and 3 tumours (χ²=11.28, d.f.=4, Pχ²=16.15, d.f.=4, Pχ²=22.45, d.f.=5, Pβ does not occur in ovarian tumours. However, overexpression of PDK1 was evident in borderline and low- to high-grade ovarian tumours and is consistent with its known role in tumorigenesis.