在 HIV 阳性男性的肛门上皮内瘤变中增殖生物标志物的表达。

Expression of proliferative biomarkers in anal intraepithelial neoplasia of HIV-positive men.

机构信息

Department of Dermatology, Ruhr-University Bochum, Bochum, Germany.

出版信息

J Am Acad Dermatol. 2010 Sep;63(3):490-8. doi: 10.1016/j.jaad.2009.08.043. Epub 2009 Dec 16.

DOI:10.1016/j.jaad.2009.08.043

PMID:20006407

Abstract

BACKGROUND

Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)-associated precursor lesion of anal carcinoma, is highly prevalent among HIV-infected individuals, especially in men having sex with men (MSM). Early diagnosis and treatment of AIN might prevent development of anal cancer.

OBJECTIVES

We aimed to evaluate the expression of 8 promising proliferative biomarkers in anal dysplasia and to compare the efficacy of these markers in diagnosing high-grade AIN.

METHODS

Immunohistochemical analysis of minichromosome maintenance proteins (MCM3, MCM4, MCM6, and MCM7), p21, Ki-67, p16, and proliferating cell nuclear antigen (PCNA) was performed in a total of 49 specimens of normal anal mucosa and high- and low-grade anal dysplasia. HPV typing for 36 high- and low-risk HPVs was performed, and high-risk HPV-DNA loads were determined by real-time polymerase chain reaction (PCR) for HPV-types 16, 18, 31, and 33.

RESULTS

A total of 392 immunohistochemical slides were analyzed in this study. In the progression from normal epithelium to high-grade dysplasia, we found significant differences in the expression of all biomarkers. A cutoff of 25% or 50% lesional immunopositivity for the 4 MCMs, Ki-67, and p16 resulted in 100% sensitivity and 100% specificity to diagnose high-grade AIN. Sensitivity and specificity of PCNA and p21 for a high-grade AIN diagnosis were lower. HPV-DNA was detectable in 100% of high-grade AIN and 87.5% of low-grade AIN lesions. All MCMs, p16, Ki-67, and PCNA, but not p21 correlated with cumulative lesional high-grade HPV-DNA loads.

LIMITATIONS

The relatively small number of samples is a limitation, especially for adequate subgroup analyses.

CONCLUSIONS

MCMs, Ki67, and p16 are reliable immunohistochemical adjuncts for diagnosing high-grade AIN.

摘要

背景

肛门上皮内瘤变（AIN）是人乳头瘤病毒（HPV）相关的肛门癌前病变，在 HIV 感染者中发病率很高，尤其是男男性行为者（MSM）。AIN 的早期诊断和治疗可能有助于预防肛门癌的发生。

目的

我们旨在评估 8 种有前途的增殖生物标志物在肛门发育不良中的表达，并比较这些标志物在诊断高级别 AIN 中的疗效。

方法

对 49 例正常肛门黏膜和高低级别肛门发育不良标本进行微小染色体维持蛋白（MCM3、MCM4、MCM6 和 MCM7）、p21、Ki-67、p16 和增殖细胞核抗原（PCNA）的免疫组化分析。对 36 种高危和低危 HPV 进行 HPV 分型，采用实时聚合酶链反应（PCR）检测 HPV16、18、31 和 33 型高危 HPV-DNA 载量。

结果

本研究共分析了 392 张免疫组化切片。从正常上皮到高级别发育不良，我们发现所有生物标志物的表达均有显著差异。4 种 MCM、Ki-67 和 p16 的病变免疫阳性率为 25%或 50%时，诊断高级别 AIN 的灵敏度和特异性均为 100%。PCNA 和 p21 诊断高级别 AIN 的敏感性和特异性较低。高级别 AIN 和低级别 AIN 病变中均能检测到 HPV-DNA。所有 MCM、p16、Ki-67 和 PCNA，但不是 p21，均与累积病变中高等级 HPV-DNA 负荷相关。