An immunohistochemical perspective of PPAR beta and one of its putative targets PDK1 in normal ovaries, benign and malignant ovarian tumours.
Peroxisome proliferator-activated receptor beta (PPAR beta) 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 PPAR beta and PDK1 with cancer, we have examined the expression of PPAR beta 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 PPAR beta and PDK1 expression. All normal ovarian tissues, benign, borderline and grade 1 tumours showed PPAR beta 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 PPAR beta staining, whereas the rest displayed some degree of nuclear and cytoplasmic staining of the scattered epithelium and stroma. The extent of epithelial and stromal PPAR beta staining was significantly different among the normal and the histological grades of tumours (chi(2)=59.25, d.f.=25, P<0.001; chi(2)=64.48, d.f.=25, P<0.001). Significantly different staining of PPAR beta was observed in the epithelium and stroma of benign and borderline tumours compared with grades 1, 2 and 3 tumours (chi(2)=11.28, d.f.=4, P<0.05; chi(2)=16.15, d.f.=4, P<0.005). In contrast, PDK1 immunostaining was absent in 9 out of 10 normal ovaries. Weak staining for PDK1 was observed in one normal ovary and 40% of benign ovarian tumours. All borderline and malignant ovarian tumours showed positive cytoplasmic and membrane PDK1 staining. Staining of PDK1 was confined to the epithelium and the blood vessels, and no apparent staining of the stroma was evident. Significantly different PDK1 staining was observed between the benign/borderline and malignant ovarian tumours (chi(2)=22.45, d.f.=5, P<0.001). In some borderline and high-grade tumours, staining of the reactive stroma was also evident. Our results suggest that unlike the colon, the endometrial, head and neck carcinomas, overexpression of PPAR beta 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.
Ahmed
N
N
Women's Cancer Research Centre, Royal Women's Hospital, Melbourne, Victoria, Australia. nuzhata@unimelb.edu.au
Riley
C
C
Quinn
M A
MA
D000368:Aged; D051242:Caveolin 1 / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000473:pathology; D010053:Ovary / Q000737:chemistry*; D048068:PPAR-beta / Q000032:analysis* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000032:analysis* / Q000502:physiology; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase
D051242:Caveolin 1; C000631429:PDK1 protein, human; D048068:PPAR-beta; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D017346:Protein Serine-Threonine Kinases