Increased expression of CCAAT/enhancer-binding protein beta in proliferative inflammatory atrophy of the prostate: relation with the expression of COX-2, the androgen receptor, and presence of focal chronic inflammation.
BACKGROUND
Proliferative inflammatory atrophy (PIA) in the prostate has been proposed to be a precursor to prostate cancer. CCAAT/enhancer-binding protein beta (C/EBPbeta) is an important transcription factor involved in cellular proliferation and differentiation. Activation of C/EBPbeta plays a crucial role during the initial stage of cyclo-oxygenase 2 (COX-2) induction by proinflammatory mediators. Overexpression of C/EBPbeta has been reported in several human tumors. Nevertheless, the C/EBPbeta expression and functions in human prostate tissue are basically unknown.


METHODS
C/EBPbeta immunohistochemical staining was performed on 45 benign prostate hyperplasia (BPH) samples. The expression of C/EBPbeta in PIA lesions and normal-appearing acini was analyzed. In addition, by using double-IHC staining, C/EBPbeta expression and the association with chronic inflammatory cell density, co-expression of COX-2 and androgen receptor (AR) were also investigated.


RESULTS
C/EBPbeta was occasionally observed in normal-appearing prostate acini (4.9% +/- 6.7%, Mean +/- SD) but was clearly overexpressed in PIA lesions (81.8% +/- 16.4%) (P < 0.0001). Atrophic glands with T-lymphocyte and macrophage inflammation expressed higher level of C/EBPbeta. Furthermore, C/EBPbeta correlated significantly with COX-2 expression. Downregulation of the AR was common in PIA and was also related to the C/EBPbeta overexpression.


CONCLUSIONS
The data demonstrated that chronic inflammation appeared to play roles in the induction of C/EBPbeta expression in prostate epithelium, which was in turn associated with increased COX-2 expression and AR downregulation. In combining with other molecular alteration in the epithelium of PIA, it is suggested that these cells might be a kind of intermediate cells and involved in the pathogenesis of prostate cancer.
Wang
Wanzhong
W
Department of Urology, Lundberg Laboratory for Cancer Research, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
Bergh
Anders
A
Damber
Jan-Erik
JE
D000368:Aged; D001284:Atrophy; D015415:Biomarkers / Q000032:analysis; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000032:analysis*; D051546:Cyclooxygenase 2 / Q000032:analysis*; D004848:Epithelium / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000473:pathology; D011472:Prostatitis / Q000378:metabolism* / Q000473:pathology*; D011944:Receptors, Androgen / Q000032:analysis*
D015415:Biomarkers; D022782:CCAAT-Enhancer-Binding Protein-beta; D011944:Receptors, Androgen; D051546:Cyclooxygenase 2