We collaborate with Agusti Toll and Ramón Pujol of the Hospital del Mar/IMIM to investigate the mechanisms leading to agressiveness of skin carcinomas.
J Dermatol Sci. 2013 Jul 15. pii: S0923-1811(13)00245-4. doi: 10.1016/j.jdermsci.2013.07.001. [Epub ahead of print]
Epithelial to mesenchymal transition markers are associated with an increased metastatic risk in primary cutaneous squamous cell carcinomas but are attenuated in lymph node metastases.
Toll A, Masferrer E, Hernández-Ruiz ME, Ferrandiz-Pulido C, Yébenes M, Jaka A, Tuneu A, Jucglà A, Gimeno J, Baró T, Casado B, Gandarillas A, Costa I, Mojal S, Peña R, de Herreros AG, García-Patos V, Pujol RM, Hernández-Muñoz I.
Servei de Dermatologia, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain; Cancer Research Program, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain.
Abstract
BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epithelial to mesenchymal transition (EMT) is a process involving loss of intercellular adhesion, acquisition of a mesenchymal phenotype and enhanced migratory potential; epithelial markers, such as E-cadherin, are down-regulated and mesenchymal proteins (Vimentin), increased.
OBJECTIVE: To investigate the expression of EMT markers in metastatic SCC (MSCC) and their corresponding metastases, and to correlate them with clinico-pathological factors associated with an increased risk of metastasis.
METHODS: We performed a retrospective study that included 146 cSCC samples (51 primary non-metastatic, 56 primary metastatic, 39 lymphatic metastases). Immunohistochemistry for E-cadherin, Vimentin, Snail, beta-catenin, Twist, Zeb1 and Podoplanin was performed.
RESULTS: Loss of membranous E-cadherin was observed in 77% cSCCs, with no differences between MSCC and non-MSCC. Among the transcriptional factors controlling EMT, no significant Snail1 expression was detected. Twist, Zeb1, Vimentin, beta-catenin and Podoplanin were significantly overexpressed in MSCCs. Twist ectopic expression in SCC13 cells induced Zeb1, Vimentin and Podoplanin expression and E-cadherin delocalization. These changes resulted in a scattered migration pattern in vitro. Expression of EMT markers was decreased in the metastases when compared with the corresponding primary tumors.
CONCLUSION: These results suggest that a partial EMT, characterized by the expression of Twist but without a total E-cadherin depletion, is involved in the acquisition of invasive traits by cSCC, but the process is downregulated in lymph node metastases.
KEYWORDS: Cutaneous squamous cell carcinoma, E-cadherin, Epithelial to mesenchymal transition, Metastasis, Twist, Vimentin
Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
