J Korean Med Sci.  2015 May;30(5):533-541. 10.3346/jkms.2015.30.5.533.

Expression of Peroxisome Proliferato Activated Receptor gamma in Prostatic Adenocarcinoma

• Park HK
• Kim H
• Kim HG
• Cho YM
• Jung WY
• Han HS
• Hwang TS
• Kwon GY
• Lim SD

• KMID: 2155464
• DOI: http://doi.org/10.3346/jkms.2015.30.5.533

Abstract

Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a ligand-activated transcription factor has been investigated as the target for cancer treatment as well as metabolic disorders. Recent studies have demonstrated that PPAR-gamma ligands are anti-tumorigenic in prostate cancer due to anti-proliferative and pro-differentiation effects. The aim of this study was to validate PPAR-gamma expression in malignant and benign prostate tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (PCR). A total of 730 prostatic adenocarcinomas (PCAs) including 63 whole sections from radical prostatectomy specimens and tissue microarrays containing 667 PCAs were subject to immunostaining for two PPAR-gamma antibodies. Twenty-five benign prostate tissues and PCAs were selected for investigating mRNA expression by quantitative real-time PCR. 10.7% of PCAs (78/730) showed cytoplasmic immunoreactivity of PPAR-gamma and no nuclear immunoreactivity was noted in PCAs. Most benign prostatic glands showed negative immunoreactivity of PPAR-gamma except for variable weak cytoplasmic staining in some glands. Nuclear immunoreactivity of PPAR-gamma was noted some central zone and verumontanum mucosal epithelium. The constitutive PPAR-gamma mRNA showed significantly lower level in PCAs compared to that in the benign tissues. There was no difference of PPAR-gamma mRNA expression between low (< or =7) and high (>7) Gleason score groups. There was no association of PPAR-gamma mRNA level or cytoplasmic immunostaining with Gleason grade or pathologic stage. Our study supported the evidence of extra-nuclear localization and nongenomic actions of PPAR-gamma. Further studies are needed to assess the functional role of PPAR-gamma and to validate its therapeutic implication in prostate cancer.

Keyword

Prostatic Neoplasms; PPAR gamma; Immunohistochemistry; Real-Time Polymerase Chain Reaction

MeSH Terms

Adenocarcinoma/metabolism/*pathology
Adult
Aged
Aged, 80 and over
*Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Male
Middle Aged
Neoplasm Staging
PPAR gamma/*genetics/*metabolism
Prostate/pathology
Prostatectomy
Prostatic Neoplasms/metabolism/*pathology
RNA, Messenger/metabolism
Real-Time Polymerase Chain Reaction
Tissue Array Analysis
PPAR gamma
RNA, Messenger

Figure

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  Fig. 1 PPAR-γ protein expression in prostate adenocarcinomas (PCAs) of tissue microarrays (TMA) by immunohistochemistry. (A) No cytoplasmic or nuclear expression (×400). (B) Diffuse cytoplasmic expression (×400).

• 

  Fig. 2 PPAR-γ protein expression in PCAs of whole sections by immunohistochemistry. (A-C) Diffuse cytoplasmic expression in carcinomas (arrow head) compared to the benign prostatic epithelial cells (*) (×400). (D) Tumor heterogeneity, negative (arrow) and positive (arrow head) (×200).

• 

  Fig. 3 PPAR-γ protein expression in benign prostate tissues by immunohistochemistry. (A) Variable weak cytoplasmic staining mainly in basal cells in benign glands. (B) Nuclear immunostaining in verumontanum mucosal epithelium. (C-D) Nuclear or cytoplasmic staining in the epithelium of benign prostatic hyperplasia (×400).

• 

  Fig. 4 PPAR-γ protein expression in positive control tissues by immunohistochemistry. Nuclear immunoreactivity in thyroid follicular carcinoma (A), urothelial carcinoma (B), and adipocytes in periprostatic tissue (C) (Original magnification: (A, C) ×400; (B) ×200).

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  Fig. 5 Expression of PPAR-γ mRNA. (A) Comparison of the mean fold change between controls, low GS (Gleason score ≤ 7) and high GS (Gleason score > 7) groups of PCAs. (B) Fold change in each sample of low GS (Low1-10) and high GS (High1-10) groups.

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