MP06-01 BASAL EPITHELIAL KERATIN 14 EXPRESSION IS ASSOCIATED WITH SQUAMOUS METAPLASIA IN URETHRAL STRICTURE DISEASE

Andrew Carey; Ethan Richmond; Bradley A. Erickson; Matthew D. Grimes

doi:10.1097/01.JU.0001009452.79331.fd.01

INTRODUCTION AND OBJECTIVE: Squamous metaplasia is a common feature of urethral stricture disease (USD), but the molecular mechanisms driving this are unknown. In response to injury/inflammation, bladder urothelium undergoes an expansion of keratin 14 (KRT 14) positive basal epithelial cells which differentiate into squamous daughter cells marked by KRT 6a and 16 to repopulate the damaged epithelium. Previously, we identified altered basal epithelial cell differentiation in lichen sclerosus related USD (LS-USD), and we speculate a similar mechanism may drive squamous metaplasia in USD. We hypothesized that epithelial KRT 14, 6a, and 16 expression will be increased in USD and LS-USD tissue compared to non-strictured urethra (NU) and positively associated with severity of histologic inflammation. METHODS: We used multiplex immunofluorescence to identify KRT 5 (a basal epithelial marker), KRT14, KRT 6a, KRT 16, and CD45 (a general immune cell marker) in NU obtained from autopsy specimens and USD/LS-USD specimens obtained from urethral biopsies and urethroplasties. QuPath software quantified the percentage of positively staining cells for each keratin marker in 3 epithelial regions/specimen and we compared these with respect to tissue type. Linear regression was used to assess the relationship between CD45+ immune cells and abundance of keratin expression. RESULTS: We analyzed 15 patients (3 NU, 6 USD, 6 LS-USD). KRT 14, 6a, and 16 expression was very low in NU and significantly higher in both USD and LS-USD specimens (p<0.05 for all) (Figure 1). Basal KRT 5 expression was similar in NU, USD, and LS-USD specimens (p=0.3). CD45+ immune cells were increased in USD and LS-USD compared to NU (p=0.003) but did not significantly correlate with KRT 14 expression (p=0.995, 0.882). CONCLUSIONS: We identified an expansion of basal epithelial KRT 14 and luminal KRT 6a and 16 expression in USD and LS-USD compared to NU. These changes occurred in the presence of inflammation but did not correlate with the degree of immune cell infiltration. These results identify basal KRT 14 expression as a feature of USD, suggest that a common molecular pathway may drive squamous metaplasia in both USD and LS-USD, and imply that restoration of homeostatic epithelial differentiation may be a therapeutic target in USD.

MP06-01 BASAL EPITHELIAL KERATIN 14 EXPRESSION IS ASSOCIATED WITH SQUAMOUS METAPLASIA IN URETHRAL STRICTURE DISEASE

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