Epithelial-to-mesenchymal transition contributes to invasion in squamous cell carcinomas originated from actinic keratosis through the differentiated pathway whereas proliferation plays a more significant role in the classical pathway

Journal of the European Academy of Dermatology and Venereology

4 years ago

Epithelial-to-mesenchymal transition contributes to invasion in squamous cell carcinomas originated from actinic keratosis through the differentiated pathway whereas proliferation plays a more significant role in the classical pathway

A Ariza, C Carrato, C Ferrándiz, M T Fernández-Figueras, L Puig, L Pérez-Roca, X Saenz-Sardà

Background Every actinic keratosis (AK) starts with atypia at the basal layers of the epidermis (AK I). Progression into invasive squamous cell carcinoma (iSCC) may occur following two main pathways, classical and differentiated. In the former, iSCC only occurs after involvement of the upper epidermal layers by atypical cells (AK III), while in the latter iSCC develops directly from AK I. In the anogenital mucosa, these two pathways are associated with differential expression of p53 and p16. Objective To explore differences between both pathways in the pathogenesis of AK, focusing on Ki67, p53, p16 and molecules that reveal epithelial mesenchymal transition. Methods Tissue microarrays representative of superficial and deep portions of 80 consecutive iSCCs (53 DP/27CP) were studied immunohistochemically using antibodies against Ki67, p53, p16, vimentin, E-cadherin, β-catenin and D2-40. The evaluation was performed by three researchers and the results compared for consensus. Results iSCCs originated through the differentiated pathway exhibited significantly lower proliferative activity (Ki67) (30% vs 46%, P=0.003) and significantly lower expression of vimentin (P<0.001), E-cadherin (P<0.001) and membranous β-catenin (P<0.001) than iSCCs developed through the classical pathway. The expression of E-cadherin and membranous β-catenin was significantly correlated (Pearson's r =0.386, Spearman's Rho<0.001). There were no significant differences regarding the expressions of p53, p16 and D2-40. Conclusion Epithelial mesenchymal transition participates in transformation from AK I into iSCC (differentiated pathway), whereas a higher proliferative capacity facilitates intraepidermal extension in the classical pathway. Podoplanin, which is also involved in tumour invasion, does not seem to play a differential role in either pathway. Finally, the absence of differences in p53 and p16 expressions is at variance with other epithelia where the classical pathway is associated with human papillomavirus infection, and can be explained by the fact that both AK pathways share identical mechanisms of actinic oncogenesis. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/jdv.14514