Darvishian Farbod, Stier Elizabeth A, Soslow Robert A, Lin Oscar
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cancer. 2006 Feb 25;108(1):66-71. doi: 10.1002/cncr.21711.
Cytology has been proposed as a potential screening tool in the evaluation of squamous anorectal disease in view of the morphologic similarities between anal and cervical squamous lesions. Previous studies have demonstrated that p16 overexpression correlates with the degree of dysplasia in the uterine cervix with promising results. Due to potential diagnostic pitfalls in anal cytology, p16 overexpression in these specimens was studied.
Patients with anorectal cytology who underwent follow-up biopsy within 1 year were selected. Forty-three anorectal cytologic specimens from 29 patients were selected. One slide of each case was destained. Avidin-biotin immunocytochemical studies with the monoclonal antibody CINtec p16(INK4a) were performed. The results of the p16 immunostaining were correlated with the histologic findings.
Twenty-eight of the 43 cases demonstrated the presence of squamous cells immunoreactive for p16 in cytology specimens. The p16-positive cells were identified in cases of low-grade squamous intraepithelial lesion (LSIL) (n = 3 cases), high-grade squamous intraepithelial lesion (HSIL) (n = 22 cases), and invasive squamous carcinoma (n = 1 case), and in 2 cases with negative follow-up biopsies. No cell immunoreactive for p16 was found in 15 cases (5 benign cases and 10 cases with either LSIL or HSIL). The sensitivity and specificity of p16 immunoreactivity in the detection of anal intraepithelial neoplasia or carcinoma were 72% and 71%, respectively. The positive and negative predictive values were 93% and 33%, respectively.
The presence of p16 immunoreactivity is a good predictor of dysplasia in anal specimens. However, the sensitivity and specificity of this marker are not high.
鉴于肛门和宫颈鳞状病变在形态学上的相似性，细胞学已被提议作为评估鳞状肛门直肠疾病的一种潜在筛查工具。先前的研究表明，p16过表达与子宫颈发育异常程度相关，结果很有前景。由于肛门细胞学检查存在潜在的诊断陷阱，因此对这些标本中的p16过表达情况进行了研究。
选择在1年内接受随访活检的肛门直肠细胞学患者。从29例患者中选取43份肛门直肠细胞学标本。对每个病例的一张玻片进行脱色处理。采用单克隆抗体CINtec p16(INK4a)进行抗生物素蛋白-生物素免疫细胞化学研究。p16免疫染色结果与组织学结果相关。
43例病例中有28例在细胞学标本中显示存在对p16免疫反应的鳞状细胞。在低级别鳞状上皮内病变（LSIL）（n = 3例）、高级别鳞状上皮内病变（HSIL）（n = 22例）、浸润性鳞状细胞癌（n = 1例）以及2例随访活检阴性的病例中发现了p16阳性细胞。15例（5例良性病例以及10例LSIL或HSIL病例）未发现对p16免疫反应的细胞。p16免疫反应性在检测肛门上皮内瘤变或癌中的敏感性和特异性分别为72%和71%。阳性和阴性预测值分别为93%和33%。
p16免疫反应性的存在是肛门标本发育异常的良好预测指标。然而，该标志物的敏感性和特异性不高。
