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

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Lana Luiza da Cruz Silva
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
Defense date:
Examining board members:
Mirian Nacagami Sotto; Valeria Aoki; Gilles Landman; Juliana Nakano de Melo; Jane Tomimori
Advisor: Mirian Nacagami Sotto

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genodermatosis, related to human beta-papillomavirus (Beta-HPV), with high risk for developing skin cancer. Claudins are transmembrane proteins expressed in epithelia and may be altered on carcinogenesis. Toward better understanding the role of Beta-HPV in cutaneous carcinogenesis, claudin expression study was performed in lesions of patients with and without EV. METHODS: A panel of anti-claudin antibodies was assembled to analyze claudins -1, -2, -3, -4, -5, -7 and -11 expression, by immunohistochemistry technique, in samples of 108 normal skin, 39 flat warts and 174 cutaneous squamous cell carcinomas (SCC), obtained from 33 patients with EV and 112 individuals without EV (not-EV - NEV). The SCC samples were organized in tissue microarrays. Statistical analysis was performed by logistic regression, aiming to verify changes in claudin profile in carcinogenesis and its relationship with age, sex and chronic sun exposure area, in patients with and without EV. RESULTS: Claudin-1 focal expression was associated with SCC (p < 0.001) and claudin-2 focal or negative expression with flat wart (p < 0.001), in EV and NEV groups. Claudin-3 focal expression was related with SCC (p < 0.001), as well as the nuclear immunostaining of claudin-3 (p < 0.001), in both groups. Additionally, chance of claudin-3 nuclear expression was 53% lower in not sun exposed areas. For claudin-5, focal expression was more common in normal skin, diffuse expression in SCC annd EV flat wart, and negative expression in NEV flat wart. The EV group showed lower chance of focal and negative expression (p < 0.001). In addition, the negativity of claudin-5 expression was associated with flat wart (p < 0.001) and lower mean age (p < 0.001). Claudins -4, -7 and -11 showed, in both groups, diffuse expression in almost all studied samples. CONCLUSIONS: Claudin-5 increasing expression was observed in cutaneous carcinogenesis and this process showed association with EV. Claudin-1 and -3 down expression were observed in cutaneous carcinomas, and claudin-2 in flat warts, however, they could not be related with Beta-HPV infection. Age and chronic sun exposure area were factors that influenced claudin-5 and claudin-3 nuclear expression, respectively (AU)

FAPESP's process: 14/15765-5 - Expression profile of claudins in flat warts and skin carcinomas in epidermodysplasia verruciformis
Grantee:Lana Luiza da Cruz Silva
Support type: Scholarships in Brazil - Doctorate (Direct)