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Urothelial Differences in the Exstrophy-Epispadias Complex: Potential Implications for Management.

Matthew Kasprenski1, Jason Michaud1, Zhiming Yang2

  • 1Division of Pediatric Urology, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland.

The Journal of Urology
|December 21, 2020
PubMed
Summary
This summary is machine-generated.

Urothelium in exstrophy-epispadias complex bladders shows significant differences from healthy controls, with reduced uroplakin-II expression and increased squamous metaplasia, especially in delayed closures.

Keywords:
bladder exstrophyepispadiasurothelium

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Area of Science:

  • Urology
  • Developmental Biology
  • Histopathology

Background:

  • The exstrophy-epispadias complex (EEC) encompasses a spectrum of congenital anomalies affecting the urinary tract.
  • Understanding the histological and molecular characteristics of the urothelium in EEC is crucial for optimizing patient management.
  • Terminal differentiation markers are key indicators of urothelial health and function.

Purpose of the Study:

  • To investigate histological differences in the urothelium of patients with EEC.
  • To assess the expression of terminal differentiation markers, specifically uroplakin-II and p63, in EEC bladders.
  • To correlate these findings with the timing of bladder closure.

Main Methods:

  • Bladder biopsies were collected from 69 pediatric EEC patients (2012-2017).
  • Histological assessment and immunohistochemical staining for uroplakin-II and p63 were performed.
  • Specimens were compared to 8 normal control bladder specimens, with blinded assessment of marker expression.

Main Results:

  • Uroplakin-II expression was significantly lower in EEC patients compared to controls (p <0.0001).
  • Delayed and repeat closures in classic bladder exstrophy showed reduced uroplakin-II expression compared to newborn closures (p=0.045).
  • p63 expression was lower in EEC patients (p <0.0001), while squamous metaplasia was higher (p=0.044), particularly in delayed closures (p <0.001).

Conclusions:

  • The urothelium in EEC bladders exhibits distinct histological and molecular profiles compared to healthy controls.
  • Reduced uroplakin-II expression and increased squamous metaplasia in EEC, particularly with delayed closure, suggest external factors may influence urothelial development.
  • These findings highlight the potential impact of the timing of primary bladder closure on urothelial growth and differentiation in EEC patients.