免疫组化染色 p16(INK4a)/Ki-67 和 L1 衣壳蛋白在 ASC-H 和 LSIL-H 病例的液基细胞学标本中的应用。

Immunostaining of p16(INK4a)/Ki-67 and L1 capsid protein on liquid-based cytology specimens obtained from ASC-H and LSIL-H cases.

机构信息

1. Department of Obstetrics and Gynecology, The Catholic University of Korea, Seoul, Korea;

出版信息

Int J Med Sci. 2013 Sep 12;10(12):1602-7. doi: 10.7150/ijms.6526. eCollection 2013.

DOI:10.7150/ijms.6526

PMID:24151431

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3804785/

Abstract

BACKGROUND

Atypical squamous cell cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and low-grade intraepithelial lesion cannot exclude high-grade squamous intraepithelial lesion (LSIL-H) are ambiguous diagnostic entities for the prediction of high-grade cervical lesion. Objective and reproducible tests for predicting high-grade cervical lesions are needed to reduce unnecessary colposcopic referrals or follow-ups.

OBJECTIVE

We aimed to identify an adequate set of adjunctive markers to predict cervical intraepithelial neoplasia grade 2+ (CIN2+) in residual liquid-based cytology specimens (LBCS).

METHODS

We conducted p16 (INK4a)/Ki-67 and L1 capsid protein immunostaining and human papillomavirus (HPV) DNA typing on 56 LBCS diagnosed with ASC-H or LSIL-H, all of which were subjected to histologic confirmation or follow-up cytologic examination.

RESULTS

Positivity for p16 (INK4a)/Ki-67 was associated with a histology of CIN2+ (P=0.047) and CIN3+ (P=0.002). Negativity for L1 capsid protein was associated with CIN2+ confirmed at follow-up (P=0.02).Positivity for high-risk HPV (HR-HPV) was associated with CIN2+ confirmed at follow-up (P=0.036) and a histology of CIN2+ (P=0.037). The sensitivity, specificity, positive predictive value, and negative predictive value for predicting follow-up CIN2+ were 76.2%, 51.4%, 48.5%, and 78.3%, respectively, for p16 (INK4a)/Ki-67 immunostaining; 95.2%, 34.3%, 46.5%, and 92.3%, respectively, for L1 capsid protein; and 66.7%, 67.7%, 54.5%, and 77.8%, respectively, for HR-HPV. The classification and regression tree analysis showed that the combined results of p16 (INK4a)/Ki-67 andL1 capsid protein immunostaining and the HR-HPV test, conducted sequentially, correctly classified 81.8% of samples (27/33)in the prediction of a histology of CIN2 + in ASC-H or LSIL-H. For determination of the histology of cervical intraepithelial neoplasia grade 3+ (CIN3+)in ASC-H or LSIL-H, we found that the combined results of p16 (INK4a)/Ki-67 and L1 capsid protein immunostaining correctly classified 78.8% (26/33) of samples.

CONCLUSIONS

p16(INK4a)/Ki-67 and L1 capsid protein immunostaining and HR-HPV testing of residual LBCS diagnosed with ASC-H or LSIL-H are useful objective biomarkers for predicting CIN2+. Immunostaining for p16(INK4a)/Ki-67 and L1 capsid protein are sufficient to predict CIN3+.

摘要

背景

非典型鳞状细胞不能排除高级别鳞状上皮内病变（ASC-H）和低级别上皮内病变不能排除高级别鳞状上皮内病变（LSIL-H）是预测高级别宫颈病变的不明确诊断实体。需要客观和可重复的测试来预测高级别宫颈病变，以减少不必要的阴道镜转诊或随访。

目的

我们旨在确定一组足够的辅助标志物来预测剩余液基细胞学标本（LBCS）中的宫颈上皮内瘤变 2+（CIN2+）。

方法

我们对 56 例诊断为 ASC-H 或 LSIL-H 的 LBCS 进行了 p16（INK4a）/Ki-67 和 L1 衣壳蛋白免疫染色以及人乳头瘤病毒（HPV）DNA 分型，所有标本均经组织学证实或随访细胞学检查。

结果

p16（INK4a）/Ki-67 阳性与 CIN2+（P=0.047）和 CIN3+（P=0.002）的组织学相关。L1 衣壳蛋白阴性与随访时的 CIN2+相关（P=0.02）。高危型 HPV（HR-HPV）阳性与随访时的 CIN2+相关（P=0.036）和 CIN2+的组织学相关（P=0.037）。用于预测随访时 CIN2+的 p16（INK4a）/Ki-67 免疫染色的敏感性、特异性、阳性预测值和阴性预测值分别为 76.2%、51.4%、48.5%和 78.3%；L1 衣壳蛋白分别为 95.2%、34.3%、46.5%和 92.3%；HR-HPV 分别为 66.7%、67.7%、54.5%和 77.8%。分类回归树分析显示，p16（INK4a）/Ki-67 和 L1 衣壳蛋白免疫染色的联合结果以及 HR-HPV 检测，依次进行，正确分类了 33 例 ASC-H 或 LSIL-H 中 81.8%（27/33）的样本的 CIN2+组织学。为了确定 ASC-H 或 LSIL-H 中的宫颈上皮内瘤变 3+（CIN3+）的组织学，我们发现 p16（INK4a）/Ki-67 和 L1 衣壳蛋白免疫染色的联合结果正确分类了 78.8%（26/33）的样本。