Protein Expression Profiles Among Lichen Sclerosus Urethral Strictures: Can Urethroplasty Success be Predicted?

Urethroplasty for lichen sclerosus (LS) strictures has a significantly higher failure rate compared to strictures due to other causes. We sought to determine predictors of urethroplasty failure in men with LS urethral stricture disease (USD) by evaluating protein expression profiles.

Urethral tissue was excised from patients with LS undergoing urethroplasty for USD at a single institution. A tissue microarray was created with cores from each sample and immunohistochemistry was performed to compare protein expression related to inflammation, cell cycle disruption, oxidative stress, hormone receptor status and infection. Stricture recurrence was defined by need for a subsequent unanticipated procedure for USD.

Fifty men with LS USD were evaluated; 31 with successful reconstruction and 19 who had recurrent strictures. Recurrent strictures expressed lower levels of several inflammatory markers, lower Ki-67 mitotic index, and significantly higher levels of VEGF compared to non-recurrent strictures.

This is the first study to use tissue protein expression to identify risk factors for urethroplasty failure among men with LS USD. Our findings suggest that LS stricture recurrences demonstrate a suppressed inflammatory response, decreased cell turnover rate, and poor oxygenation and nutrient delivery. Prospective studies are needed to clarify the role of these pathways in the pathophysiology of LS USD, to determine if preoperative biopsy can predict urethroplasty success, to help counsel patients, and to develop future treatments.

The Journal of urology. 2019 Oct 17 [Epub ahead of print]

Alison C Levy, Matthew Moynihan, Jennifer A Bennett, Travis Sullivan, Kristian Stensland, Brendan M Browne, Ariel Fredrick, Jaime A Cavallo, Elizabeth Pagura, Rafael Tua-Caraccia, Kimberly M Rieger-Christ, Alex J Vanni

Lahey Hospital and Medical Center, Burlington, Massachusetts., Tufts University School of Medicine, Boston, Massachusetts.