Departament of Dermatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
Departament of Pathology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
Sci Rep. 2020 Jun 9;10(1):9268. doi: 10.1038/s41598-020-66065-y.
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.
疣状表皮发育不良(EV)是一种与人类β-乳头瘤病毒(β-HPV)相关的遗传性皮肤病,具有较高的皮肤鳞状细胞癌(cSCC)风险。紧密连接蛋白是上皮细胞中表达的跨膜蛋白,在癌变过程中可能会发生改变。为了更好地了解β-HPV 在皮肤癌变中的作用,对患有和不患有 EV 的患者的病变进行了这项紧密连接蛋白表达研究。在这项研究中,通过应用免疫组织化学技术分析了 108 例正常皮肤、39 例扁平疣和 174 例 cSCC 样本中的 claudin-1、-2、-3、-4、-5、-7 和 -11 的表达。cSCC 样本组织成组织微阵列。我们发现,claudin-1 和 claudin-3 的局灶性表达与 cSCC 相关(p<0.001),而 claudin-2 的局灶性或阴性表达与扁平疣相关(p<0.001),在 EV 和 NEV(非 EV)组中。对于 claudin-5,EV 组显示出较低的局灶性和阴性表达机会(p<0.001),其阴性表达与扁平疣相关(p<0.001),并且平均年龄较低(p<0.001)。claudin-4、-7 和 -11 在几乎所有研究样本中均表现为弥漫性表达。我们的研究结果表明,在正常皮肤、扁平疣和 cSCC 中观察到的 claudin-5 高表达与 EV 相关。还观察到 claudin-1 和 claudin-3 的下调表达,但它们可能与β-HPV 感染无关。