Altered Epithelial Differentiation in Urethral Stricture Disease Is Characterized by Increased Keratin 14, 6A, and 16...

To test the hypothesis that basal epithelial keratin 14 (KRT14) expression and superficial KRT6a and KRT16 expression are increased in urethral stricture disease (USD) compared to non-strictured urethra (NU), and are positively associated with the severity of immune cell infiltration.

We used multiplexed fluorescent immunohistochemistry to identify KRT5 (a basal epithelial marker), KRT14, KRT6a, KRT16, and CD45 (an inflammatory cell marker) in NU obtained from autopsy decedents and USD specimens with and without lichen sclerosus (LS-USD) obtained from urethral biopsy and urethroplasty. The relative abundance of positively staining cells was compared with respect to tissue/stricture types and immune cell infiltration using Mann-Whitney U tests and linear regression.

We analyzed 15 patients (3 Normal, 6 USD, 6 LS-USD). Expression of KRT14, 6a, and 16 was significantly higher in both USD and LS-USD compared to NU (P < .05 for all). KRT 14 expression was not associated with histologic inflammation in either (P = .995) or LS-USD (P = .672).

We identified increased expression of epithelial KRT14, 6a, and 16 in USD and LS-USD compared with NU. This pattern of altered epithelial differentiation in the setting of chronic inflammation mirrors changes seen in response to acute epithelial injury and subsequent chronic inflammation in other organ systems. These hypothesis-generating results suggest further study of the downstream effects of these changes, including increased epithelial permeability due to compromised barrier function.