title: A switch from epithelial to mesenchymal properties correlates with lymphovascular invasion in squamous cell carcinoma of the penis.
abstract: 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.
authors.affiliation: Department of Urology, St. Elisabeth Clinic Straubing, Straubing, Germany. Electronic address: matthias.may@klinikum-straubing.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: May
authors.affiliation: Department of Urology, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Brookman-May
authors.affiliation: Departments of Urology, Regensburg University, St. Josef Medical Centre, Regensburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Burger
authors.affiliation: Institute of Pathology at the HELIOS Clinic Bad Saarow, Charité-University Medicine Academic Teaching Hospital, Bad Saarow, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Koch
authors.affiliation: Departments of Urology, Regensburg University, St. Josef Medical Centre, Regensburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Otto
authors.affiliation: Departments of Urology, Regensburg University, St. Josef Medical Centre, Regensburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Bründl
authors.affiliation: Department of Pathology, Forensic Medicine and Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Albrecht
authors.affiliation: Departments of Urology, Regensburg University, St. Josef Medical Centre, Regensburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Denzinger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001808:Blood Vessels / Q000473:pathology*; D015820:Cadherins / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D058750:Epithelial-Mesenchymal Transition; D005858:Germany; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D042601:Lymphatic Vessels / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D015588:Observer Variation; D010412:Penile Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014746:Vimentin / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D014746:Vimentin
keywords: Cadherin switch; Epithelial-to-mesenchymal transition; Immunohistochemistry; Lymphovascular invasion; Squamous cell carcinoma of the penis; Targeted therapies