Institute of Pathology, Medical University Graz, Graz, Austria.
J Am Acad Dermatol. 2013 Jul;69(1):73-81. doi: 10.1016/j.jaad.2012.12.973. Epub 2013 Mar 6.
Penile squamous cell carcinomas (SCC) arise either through transforming infections with human papillomavirus (HPV) or independent of HPV, often in the background of lichen sclerosus (LS) and lichen planus (LP). Despite impact on therapy and prognosis, etiologic stratifications are missing in most histological diagnoses and publications about penile cancers/precursors.
Classification of penile lesions into HPV-induced or HPV-negative via immunohistochemical demonstration of p16(ink4a) overexpression, a surrogate marker for transforming HPV-high-risk infections, and p53 expression in the absence of p16(ink4a) overexpression.
Archival formalin-fixed material of 123 invasive penile cancers and 43 pre-invasive lesions was evaluated for the presence of LS, LP, 28 HPV genotypes, and expression of p53 and p16(ink4a).
Seventy-two of 123 SCCs and 33 of 43 pre-invasive lesions showed p16(ink4a) overexpression independent of HPV-HR genotypes involved; 66 of 72 SCCs and 29 of 43 precursor lesions revealed a single HPV-high-risk-genotype (HPV-HR16 in 76% followed by HPV33, HPV31, HPV45, HPV18, HPV56); 5 of 72 SCCs and 4 of 43 precursor lesions revealed multiple HPV-HR-genotypes. One SCC revealed HPV-LR and HR-DNA. Fifty-one of 123 SCCs and 10 precursor lesions were p16(ink4a) negative, but showed nuclear p53 expression in tumor cells and basal keratinocytes. Forty-nine of 51 SCCs and 10 of 10 precursor lesions lacked HPV DNA. Two of 51 SCCs contained HPV18 and HPV45 DNA, respectively, but p16(ink4a) negativity classified them as non-HPV-induced. Twenty-seven of 51 SCCs showed peritumoral LS, 13 of 51 SCCs showed peritumoral LP, and 11 SCCs revealed no peritumoral tissue. Histologically, HPV-negative precursors showed hyperkeratotic, verrucous, atrophic, and basaloid differentiation.
This was a retrospective study.
p16(ink4a) overexpression identifies HPV-HR-induced penile carcinogenesis independent of HPV-HR genotype. p53 expression along with p16(ink4a) negativity identifies HPV-negative cancers. Correct etiologic classification of penile lesions during diagnostic work-up allows optimal therapy decisions.
阴茎鳞状细胞癌（SCC）的发生要么是由于人乳头瘤病毒（HPV）的转化感染，要么是独立于 HPV 的，通常发生在硬化性苔藓（LS）和扁平苔藓（LP）的背景下。尽管对治疗和预后有影响，但大多数关于阴茎癌/前体的组织学诊断和出版物都缺乏病因分层。
通过免疫组织化学显示 p16(ink4a)过表达，将阴茎病变分类为 HPV 诱导或 HPV 阴性，p16(ink4a)过表达是 HPV 高危感染的替代标志物，而 p53 表达则缺乏 p16(ink4a)过表达。
评估了 123 例侵袭性阴茎癌和 43 例前病变的存档福尔马林固定材料，以评估 LS、LP、28 种 HPV 基因型以及 p53 和 p16(ink4a)的表达。
72 例 SCC 和 33 例前病变显示 p16(ink4a)过表达，与 HPV-HR 型无关；66 例 SCC 和 29 例前病变显示单一 HPV 高危型（HPV-HR16 占 76%，其次是 HPV33、HPV31、HPV45、HPV18、HPV56）；5 例 SCC 和 4 例前病变显示多种 HPV-HR 型。1 例 SCC 显示 HPV-LR 和 HR-DNA。51 例 SCC 和 10 例前病变 p16(ink4a)阴性，但肿瘤细胞和基底角质形成细胞显示核 p53 表达。49 例 SCC 和 10 例前病变缺乏 HPV DNA。2 例 SCC 分别含有 HPV18 和 HPV45 DNA，但 p16(ink4a)阴性将其归类为非 HPV 诱导。51 例 SCC 中有 27 例显示肿瘤周围 LS，51 例 SCC 中有 13 例显示肿瘤周围 LP，11 例 SCC 显示无肿瘤周围组织。组织学上，HPV 阴性前体表现为过度角化、疣状、萎缩和基底样分化。
这是一项回顾性研究。
p16(ink4a)过表达鉴定 HPV-HR 诱导的阴茎癌发生，与 HPV-HR 基因型无关。p53 表达结合 p16(ink4a)阴性鉴定 HPV 阴性癌症。在诊断过程中正确的病因学分类可以做出最佳的治疗决策。
