Claudin expression profile in flat wart and cutaneous squamous cell carcinoma in epidermodysplasia verruciformis

Lana Luiza Da Cruz Silva,Mirian N Sotto,Ilana Halpern,Walmar Roncalli Pereira De Oliveira,Naiura Vieira Pereira,Claudia Kwei-Fong Dai Tanabe,Mayra Servilha Grion Mattos

doi:10.1038/s41598-020-66065-y

Lana Luiza Da Cruz Silva, Mirian N Sotto + Show 5 more

Open Access

https://doi.org/10.1038/s41598-020-66065-y

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Abstract

Epidermodysplasia verruciformis (EV) is a genodermatosis related to human beta-papillomavirus (beta-HPV), with a high risk of cutaneous squamous cell carcinoma (cSCC). Claudins are transmembrane proteins expressed in epithelia and may be altered during carcinogenesis. For a better understanding of the role of beta-HPV in cutaneous carcinogenesis, this claudin expression study was conducted on lesions of patients with and without EV. In this study, claudins-1, -2, -3, -4, -5, -7 and -11 expressions were analyzed by applying the immunohistochemistry technique, in samples of 108 normal skin, 39 flat warts and 174 cSCC. The cSCC samples were organized in tissue microarrays. We found that claudin-1 and claudin-3 focal expressions were associated with cSCC (p < 0.001), and claudin-2 focal or negative expression with flat wart (p < 0.001), in EV and NEV (non-EV) groups. For claudin-5, EV group showed a lower chance of focal and negative expression (p < 0.001), and its negative expression was associated with flat wart (p < 0.001) and lower mean age (p < 0.001). Claudins-4, -7 and -11 showed a diffuse expression in almost all studied samples. Our findings suggest that claudin-5 increased expression observed on normal skin, flat wart and cSCC showed association with EV. Claudin-1 and -3 down expression were also observed, but they could not be related to beta-HPV infection.

Highlights

Epidermodysplasia verruciformis (EV) is a genodermatosis related to human beta-papillomavirus, with a high risk of cutaneous squamous cell carcinoma
EV is a rare inherited genodermatosis with beta-HPV susceptibility and predisposition to cutaneous carcinomas, which usually occurs during the fourth decade[2]
There is no difference regarding gender[1,3], in our sample, men were more prevalent among EV patients

Summary

Introduction

Epidermodysplasia verruciformis (EV) is a genodermatosis related to human beta-papillomavirus (betaHPV), with a high risk of cutaneous squamous cell carcinoma (cSCC). Our findings suggest that claudin-5 increased expression observed on normal skin, flat wart and cSCC showed association with EV. Claudins are involved in the cytoskeletal maintenance, cell signaling and TJ permeability[8] They are expressed in normal epithelium, where they show different profiles, which are responsible for the heterogeneity of paracellular characteristic among epithelia[9]. In epithelial tumorigenesis, both decreased and increased claudin expression have been associated with a biological behavior of the tumor, including involvement in survival and invasion processes of neoplastic cells[10,11]. We consider interesting to analyze claudins expression pattern in EV, throughout the progression of normal skin to flat wart and cutaneous SCC, comparing them to normal skin, flat warts and neoplastic processes from individuals without EV

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