Abstract：
Netherton syndrome (NS) is a rare genetic disease presenting with ichthyosiform erythroderma, hair alterations and atopy. NS is due to SPINK5 gene mutations, which cause absent or decreased expression of the encoded protein lymphoepithelial Kazal-type-related inhibitor (LEKTI) in all stratified epithelia. We report a 43-year-old man affected with NS, who developed several squamous and basal cell carcinomas on the face, ears and scalp and papillomatous lesions of hips, groin and genitoanal area. Molecular analysis of the SPINK5 gene revealed homozygosity for the recurrent mutation c.238dupG. Human papillomavirus (HPV) DNA detection and genotyping on patient skin carcinomas and hyperplastic lesions found betapapillomavirus DNA in 10 of 12 (83%) carcinomas and in a hip papilloma, with multiple betapapillomavirus types being identified. Immunohistochemistry showed upregulated expression of p16(INK4a) protein in nine of 12 (75%) patient carcinomas, in line with findings reported in HPV-related cancers. LEKTI and filaggrin immunostaining was strongly decreased in patient skin. A published work search for NS cases with skin cancers and HPV infection identified 15 NS patients, five of them showing mucosal or cutaneous HPV infection. Overall, our results confirm the increased susceptibility to skin carcinomas of some NS patients and provide further evidence of an association between HPV and non-melanoma skin cancers in NS. The highly impaired skin barrier function, hallmark of NS, could facilitate HPV infection, in turn increasing the risk for cancer development.
摘要：
Netherton综合征（NS）是一种罕见的遗传性疾病，表现为鱼鳞状红皮病，头发的改变和过敏。NS是由于SPINK5基因突变，导致所有分层上皮中编码的蛋白淋巴上皮Kazal型相关抑制剂（LEKTI）的表达缺失或降低。我们报告了一名43岁的男子患有NS，他在脸上患上了几种鳞状细胞癌和基底细胞癌，耳朵和头皮和臀部乳头状瘤病变，腹股沟和生殖器区域。SPINK5基因的分子分析揭示了复发性突变c.238dupG的纯合性。对患者皮肤癌和增生性病变的人乳头瘤病毒（HPV）DNA检测和基因分型在12个（83％）癌中的10个（83％）和髋部乳头状瘤中发现了β-乳头状瘤病毒DNA，与多种β-apillomavirus类型被鉴定。免疫组织化学显示p16（INK4a）蛋白在12例患者癌中有9例（75％）表达上调，与HPV相关癌症的研究结果一致.患者皮肤中的LEKTI和聚丝蛋白免疫染色强烈降低。已发表的对患有皮肤癌和HPV感染的NS病例的研究发现了15例NS患者，其中5例表现为粘膜或皮肤HPV感染。总的来说,我们的结果证实了某些NS患者对皮肤癌的易感性增加,并进一步证明了HPV与非黑色素瘤皮肤癌的相关性.高度受损的皮肤屏障功能，NS的标志，可以促进HPV感染，反过来增加癌症发展的风险。
