DDL Diagnostic Laboratory, Visseringlaan, Rijswijk.
Department of Pathology, Weill Cornell Medical College, New York, NY.
Am J Surg Pathol. 2018 Apr;42(4):463-471. doi: 10.1097/PAS.0000000000000984.
Progression of anal intraepithelial neoplasia (AIN) involves transition from productive to transforming human papillomavirus (HPV) infection. Grading aims to distinguish productive low-grade AIN from high-grade anal intraepithelial neoplasia (HGAIN) with risk of cancer. We describe immunohistochemical patterns in AIN adding a novel marker for initiation of the productive phase of the HPV life cycle (panHPVE4) to those for cell cycle activity (Ki-67) and transforming activity of HPVE7 gene (p16). We studied 67 anal biopsies for suspected anal neoplasia (17 normal, 15 AIN1, 20 AIN2, 15 AIN3) from 54 men who have sex with men at New York Presbyterian Hospital, USA. Two pathologists generated consensus AIN and immunogrades. Whole tissue and laser capture microdissection samples from multiple HPV-infected biopsies were tested for HPV with SPF10-PCR-DEIA-LiPA25, version 1. (Para)basal Ki-67 expression distinguished normal from AIN (≥lower-third Ki-67) with sensitivity 0.92 and specificity 1.0. Ki-67 did not distinguish grades of AIN. Null/patchy p16 versus diffuse ≥lower-third patterns discriminated HGAIN (sensitivity, 1.0; specificity, 0.84). There was marked heterogeneity in E4 expression within HGAIN. Most AIN2 (14/20) was E4 versus 0/15 AIN3 (sensitivity, 0.70; specificity 1.0). HPV was detected in 63 (94%) biopsies, with 49 (77.8%) high-risk HPV. HPV16 was the most frequent (13%). Multiple HPV genotypes were found in 15 (24%) biopsies and laser capture microdissection -polymerase chain reaction confirmed specific HPV types in E4 +/- AIN. Although Ki-67 discriminated AIN and p16 HGAIN, E4/p16 staining shows that most AIN2 is different from transformed AIN3 in showing both entry into productive HPV infection and transforming activity.
肛门上皮内瘤变（AIN）的进展涉及从有生产力到转化人乳头瘤病毒（HPV）感染的转变。分级旨在区分有生产力的低级别 AIN 与有癌症风险的高级别肛门上皮内瘤变（HGAIN）。我们描述了 AIN 的免疫组织化学模式，除了用于细胞周期活性（Ki-67）和 HPV E7 基因转化活性（p16）的标记物外，还添加了用于 HPV 生命周期有生产力阶段启动的新型标记物（panHPVE4）。我们研究了来自美国纽约长老会医院的 54 名男男性行为者的 67 例疑似肛门肿瘤的肛门活检（17 例正常，15 例 AIN1，20 例 AIN2，15 例 AIN3）。两位病理学家对 AIN 和免疫等级达成共识。使用 SPF10-PCR-DEIA-LiPA25，版本 1 对来自多个 HPV 感染活检的整个组织和激光捕获微解剖样本进行 HPV 检测。（旁）基底 Ki-67 表达将正常与 AIN（≥下三分之一 Ki-67）区分开来，敏感性为 0.92，特异性为 1.0。Ki-67 不能区分 AIN 的等级。空斑/点状 p16 与弥漫性≥下三分之一模式区分 HGAIN（敏感性为 1.0，特异性为 0.84）。在 HGAIN 中，E4 表达存在明显的异质性。大多数 AIN2（14/20）为 E4 阳性，而 AIN3 为 0/15（敏感性为 0.70，特异性为 1.0）。在 63 例（94%）活检中检测到 HPV，其中 49 例（77.8%）为高危 HPV。HPV16 是最常见的（13%）。15 例（24%）活检中发现多种 HPV 基因型，激光捕获微解剖-聚合酶链反应在 E4 +/-AIN 中证实了特定的 HPV 类型。尽管 Ki-67 区分了 AIN 和 p16 HGAIN，但 E4/p16 染色表明，大多数 AIN2 与转化的 AIN3 不同，它既进入有生产力的 HPV 感染，又具有转化活性。
