Myofibroblast-dominant proliferation associated with severe fibrosis in bulbar urethral strictures.

Abstract

OBJECTIVES:

Myofibroblast-dominant proliferation (relative to fibroblast proliferation) is the key process in urethral fibrosis, but its association with clinical features is not understood. We conducted a histological analysis of urethral strictures and examined the association between myofibroblast proliferation and stricture characteristics.

METHODS:

Formalin-fixed, paraffin-embedded urethral sections sliced axially from 175 male patients with bulbar urethral strictures were retrospectively analyzed. All patients underwent excision and primary anastomosis between September 2008 and January 2021 by a surgeon (AH). Masson's trichrome stain was used to estimate the area of fibrosis. Corresponding unstained slides with the largest area of fibrosis were selected and double-immunostained with anti-smooth muscle actin (SMA) and anti-TE-7 mouse monoclonal antibodies for the assessment of myofibroblasts and fibroblasts, respectively. The ratio of the number of SMA-positive cells to the number of TE-7-positive cells (SMA/TE-7 ratio) was calculated.

RESULTS:

The area of fibrosis in strictures due to perineal trauma (n = 85, median 108.9 mm2 ) was significantly larger than that in non-traumatic strictures (n = 90, median 42.9 mm2 , p < 0.0001). The area of fibrosis positively correlated with SMA expression (r = 0.35, p < 0.0001) and the SMA/TE-7 ratio (r = 0.36, p < 0.0001), but not with TE-7 expression (r = -0.01, p = 0.75). In a multivariate linear regression model, traumatic etiology (standard coefficient 0.37, t value 3.9, p < 0.0001) and increased SMA expression (standard coefficient 0.17, t value 2.1, p = 0.03) were the predictors of wide fibrosis area.

CONCLUSIONS:

Myofibroblast-dominant proliferation may contribute to the pathogenesis of severe urethral fibrosis.

• Authors: Yusuke Hirano, Akio Horiguchi, Kenichiro Ojima, Ryuichi Azuma, Masayuki Shinchi, Kenichi Ito, Kosuke Miyai
• Journal: International journal of urology : official journal of the Japanese Urological Association (Int J Urol) Vol. 30 Issue 1 Pg. 107-112 (01 2023) ISSN: 1442-2042 [Electronic] Australia
• PMID: 36124737 (Publication Type: Journal Article)
• Copyright: © 2022 The Japanese Urological Association.

Topics

• Animals
• Mice
• Male
• Urethral Stricture (etiology, surgery)
• Myofibroblasts
• Constriction, Pathologic (surgery)
• Retrospective Studies
• Urethra (surgery)
• Fibrosis
• Cell Proliferation
• Treatment Outcome
• Urologic Surgical Procedures, Male