Švajdler Marián, Mezencev Roman, Kašpírková Jana, Kacerovská Denisa, Kazakov Dmitry V, Ondič Ondrej, Michal Michal
*Šikl's Department of Pathology, the Faculty of Medicine and Faculty Hospital in Pilsen, Charles University in Prague, Pilsen, Czech Republic; †Bioptická laboratoř, s.r.o., Pilsen, Czech Republic; ‡Department of Pathology, Louis Pasteur University Hospital, Košice, Slovakia; and §Integrated Cancer Research Center, School of Biology and Parker H. Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA.
Am J Dermatopathol. 2016 Oct;38(10):751-7. doi: 10.1097/DAD.0000000000000530.
An increased rate of second nonmelanoma skin cancers is found in immunocompromised patients. Epidemiological and molecular data implicate ultraviolet radiation as the major risk factor. In addition, there is increasing evidence supporting the role of human papillomavirus (HPV) in the pathogenesis of premalignant and malignant skin lesions in both immunocompetent and immunocompromised patients. In a retrospective cross-sectional study, the authors examined the expression of p16 by immunohistochemistry and the presence of mucosal (α-genus) and cutaneous/epidermodysplasia verruciformis (β-genus) HPV DNA by polymerase chain reaction in 29 biopsy specimens of extragenital/extraungual Bowen disease (BD) from 24 Eastern European white immunocompromised patients. Furthermore, the author evaluated the association between the expression of p16 protein and the presence of HPV DNA. Among 25 specimens from 21 patients evaluable by polymerase chain reaction, HPV DNA was detected in 10 (40%) BD lesions from 9 patients. Beta-HPV predominated over alpha-HPV types. Among 29 immunohistochemically evaluable BD specimens, 22 lesions (∼76%) from 20 patients were scored as p16 positive. HPV DNA-positive and HPV DNA-negative lesions displayed the same proportion of p16 positivity (80%) and no correlation was found between the HPV DNA presence and the p16 expression status. Our pilot study demonstrated that β-HPV infections predominate in BD cases diagnosed among immunocompromised patients, although high- and low-risk mucosal (alpha) HPV genotypes may be detected in a minority of cases. In contrast to anogenital HPV-associated lesions, positive p16 expression is not a reliable marker of high-risk α-HPV infection in BD cases, as it can be also detected in β-HPV infected and HPV-negative cases.
免疫功能低下的患者发生第二例非黑色素瘤皮肤癌的几率增加。流行病学和分子数据表明紫外线辐射是主要风险因素。此外，越来越多的证据支持人乳头瘤病毒（HPV）在免疫功能正常和免疫功能低下患者的癌前和恶性皮肤病变发病机制中的作用。在一项回顾性横断面研究中，作者通过免疫组织化学检测了24例东欧白人免疫功能低下患者的29份生殖器外/指甲外鲍恩病（BD）活检标本中p16的表达，并通过聚合酶链反应检测了黏膜（α属）和皮肤/疣状表皮发育异常（β属）HPV DNA的存在。此外，作者评估了p16蛋白表达与HPV DNA存在之间的关联。在21例可通过聚合酶链反应评估的患者的25份标本中，在9例患者的10个（40%）BD病变中检测到HPV DNA。β-HPV比α-HPV类型更常见。在29份可通过免疫组织化学评估的BD标本中，20例患者的22个病变（约76%）被评为p16阳性。HPV DNA阳性和HPV DNA阴性病变显示出相同比例的p16阳性（80%），并且未发现HPV DNA的存在与p16表达状态之间存在相关性。我们的初步研究表明，在免疫功能低下患者中诊断出的BD病例中，β-HPV感染占主导，尽管在少数病例中可能检测到高危和低危黏膜（α）HPV基因型。与肛门生殖器HPV相关病变不同，p16阳性表达在BD病例中不是高危α-HPV感染的可靠标志物，因为在β-HPV感染和HPV阴性病例中也可以检测到。
