Division of Pediatric Urology, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Urol. 2021 May;205(5):1460-1465. doi: 10.1097/JU.0000000000001510. Epub 2020 Dec 21.
The authors examined the urothelium of exstrophy-epispadias complex spectrum patients for histological differences and expression of terminal markers of urothelial differentiation.
Between 2012 and 2017 bladder biopsies were obtained from 69 pediatric exstrophy-epispadias complex patients. These specimens were compared to bladder specimens from normal controls. All bladder specimens underwent histological assessment followed by immunohistochemical staining for uroplakin-II and p63. Expression levels of uroplakin-II and p63 were then assessed by a blinded pathologist.
Forty-three classic bladder exstrophy biopsies were obtained (10 newborn closures, 22 delayed closures, and 11 repeat closures). Additional biopsies from 18 cloacal exstrophy patients and 8 epispadias patients were also evaluated. These specimens were compared to 8 normal control bladder specimens. Overall, uroplakin-II expression was lower in exstrophy-epispadias complex patients compared to controls (p <0.0001). Among classic bladder exstrophy patients, there was reduced expression of uroplakin-II in the delayed and repeat closures in comparison to newborn closures (p=0.045). Expression of p63 was lower in patients with exstrophy-epispadias complex compared to controls (p <0.0001). Expression of p63 was similar among classic bladder exstrophy patients closed as newborns when compared to delayed or repeat closures. Classic bladder exstrophy patients had a higher rate of squamous metaplasia when compared to controls (p=0.044). Additionally, there was a higher rate of squamous metaplasia in the patients undergoing delayed closure in comparison to those closed in the newborn period (p <0.001).
The urothelium in the exstrophy-epispadias complex bladder is strikingly different than that of healthy controls. Uroplakin-II expression is greatly reduced in exstrophy-epispadias complex bladders and is influenced by the timing of bladder closure. Reduced uroplakin-II expression and increased rates of squamous metaplasia in exstrophy-epispadias complex patients undergoing delayed closure suggests that exposure of the urothelium may induce these changes. These findings shed light on the molecular changes in exstrophy-epispadias complex bladders and may have implications on the appropriate timing of primary bladder closure, as those closed in the newborn period appear to have a greater potential for growth and differentiation.
作者研究了外生殖器-尿道上裂综合征患者的尿路上皮，以检查其组织学差异和尿路上皮分化的终末标志物的表达。
2012 年至 2017 年间，作者从 69 名小儿外生殖器-尿道上裂综合征患者中获得了膀胱活检标本。将这些标本与正常对照组的膀胱标本进行了比较。所有膀胱标本均进行了组织学评估，然后进行了尿路上皮分化的尿路上皮素-II 和 p63 的免疫组织化学染色。然后由一位盲法病理学家评估尿路上皮素-II 和 p63 的表达水平。
作者获得了 43 例经典膀胱外翻活检标本（10 例新生儿闭合，22 例延迟闭合，11 例重复闭合）。还评估了 18 例直肠外翻患者和 8 例尿道上裂患者的额外活检标本。将这些标本与 8 例正常对照组的膀胱标本进行了比较。总体而言，与对照组相比，外生殖器-尿道上裂综合征患者的尿路上皮素-II 表达水平较低（p<0.0001）。在经典膀胱外翻患者中，与新生儿闭合相比，延迟和重复闭合的尿路上皮素-II 表达减少（p=0.045）。与对照组相比，患有外生殖器-尿道上裂综合征的患者的 p63 表达较低（p<0.0001）。与新生儿闭合的经典膀胱外翻患者相比，延迟或重复闭合的患者的 p63 表达相似。与对照组相比，经典膀胱外翻患者的鳞状化生发生率更高（p=0.044）。此外，与新生儿期闭合的患者相比，延迟闭合的患者鳞状化生发生率更高（p<0.001）。
外生殖器-尿道上裂综合征膀胱的尿路上皮与健康对照组明显不同。外生殖器-尿道上裂综合征患者的尿路上皮素-II 表达大大降低，且受膀胱闭合时间的影响。外生殖器-尿道上裂综合征患者延迟闭合时尿路上皮素-II 表达降低和鳞状化生发生率增加表明，尿路上皮的暴露可能会引起这些变化。这些发现揭示了外生殖器-尿道上裂综合征患者膀胱中的分子变化，并可能对外生殖器-尿道上裂综合征患者膀胱的适当闭合时间产生影响，因为新生儿期闭合的患者似乎具有更大的生长和分化潜力。
