PD16-06: Shift change of the activated complement pathway in the fibrotic process associated with progression of benign prostatic hyperplasia

Junya Hata*, Yusuke Kirihana, Tomoyuki Kumekawa, Hiroki Natsuya, Yusuke Hakozaki, Syunsuke Yoshioka, Hitomi Imai, Kanako Matsuoka, Tomoyuki Koguchi, Yuichi Sato, Hidenori Akaihata, Masao Kataoka, Yoshiyuki Kojima, Fukushima, Japan

Introduction: In a previous study, we reported that complement activation by an autoimmune reaction was associated with the growth process of benign prostatic hyperplasia (BPH). On the other hand, BPH was reported to show a histological transition from smooth muscle-dominant type to fibrous-dominant type as it becomes more severe. Therefore, we hypothesized that activation of complement pathways might be associated with the fibrous process of BPH with progression. In this study, to clarify the activated complement pathway in the fibrous process of BPH with progression, we analyzed the histological severity and the expression of complement components using human fibrous BPH tissues.

Methods: The subjects were 56 histological BPH patients who underwent prostate needle biopsy due to high PSA levels in our institutions (mean age 68.6 ± 6.5 years). BPH patients were divided into two histological groups, fibromuscular type and fibrous type, by hematoxylin-eosin and elastica-Masson staining. Complement expression function analysis was performed by immunohistochemical staining using C3, factor B, and C5b-9 antibody, and the occupancy ratio of the stained region was calculated.

Results: Twenty-seven cases (48.2%) were classified as fibromuscular type, and 29 cases (51.8%) were classified as fibrous type. The proportion of fibrous components was significantly lower in the fibromuscular type than in the fibrous type (fibromuscular type 36.0 ± 12.9%, fibrous type 61.1 ± 11.7% (p < 0.01)). In the expression analyses of complement components, factor B was not significantly different between the two groups, whereas C3 (fibromuscular type 10.7 ± 8.2%, fibrous type 16.4 ± 12.7%) and C5b-9 (fibromuscular type 15.9 ± 6.2%, fibrous type 17.6 ± 9.2%) were significantly upregulated in fibrous type compared to fibromuscular type (p = 0.04, p = 0.04). Furthermore, abundant infiltration of inflammatory cells was observed in the fibromuscular type (p = 0.03).

Conclusions: In the fibrous process of BPH from fibromuscular type to fibrous type histologically, the inflammatory amplification loop enhancement by complement alternative pathway activation promotes the fibrosis of BPH, and finally shifts to fibrotic BPH. These results suggested that shift change to complement late pathway activation was involved in the progression of fibrous BPH.

Source of Funding: None