A switch from epithelial to mesenchymal properties correlates with lymphovascular invasion in squamous cell carcinoma of the penis.

The purpose of the study was to assess the incidence and prognostic role of epithelial-to-mesenchymal-transition (EMT) in squamous cell carcinoma of the penis (SCCP). Sixty tumor specimens of surgically treated SCCP patients characterized by a central histopathologic review were stained with antibodies against E-cadherin, N-cadherin, β-catenin, and vimentin. Staining profiles were scored by two independent raters, and correlated with pertinent clinical and pathological parameters and cancer-specific mortality (CSM; median follow-up: 34 months, interquartile range: 6-60 months). Correlation statistics proved good interobserver agreement in staining evaluation (K-values between 0.62 and 1.00, all p<0.001). Based on consensus decision between both raters, 36 study cases (60%) showed a switch from E-cadherin to N-cadherin (as a hallmark of EMT), which correlated with the presence of lymphovascular invasion (ρ=0.287, p=0.026) while failing to interfere with CSM. Although cadherin switch was correlated with a loss of membranous β-catenin expression (ρ=0.629, p<0.001), none of the study cases showed nuclear β-catenin expression, and only three EMT cases (8.3%) had tumor buds revealing vimentin expression. Our data suggest that roughly half of surgically treated SCCP cases exhibit EMT, a parameter correlating with lymphovascular invasion. However, further studies are clearly needed to validate the so far unresolved possible role of cadherin switch in terms of predicting nodal spread in patients with SCCP. Moreover, the apparently complex mechanisms driving EMT in SCCP should be explored by future studies, as knowledge about these might provide a so far unexploited basis for the development of novel targeted therapies against SCCP with metastatic dissemination.