液基细胞学样本中p16INK4a染色宫颈鳞状细胞的核评分评估。

Evaluation of a nuclear score for p16INK4a-stained cervical squamous cells in liquid-based cytology samples.

作者信息

Wentzensen Nicolas, Bergeron Christine, Cas Frederic, Eschenbach Denise, Vinokurova Svetlana, von Knebel Doeberitz Magnus

机构信息

Institute of Molecular Pathology, University of Heidelberg, Heidelberg, Germany.

出版信息

Cancer. 2005 Dec 25;105(6):461-7. doi: 10.1002/cncr.21378.

DOI:10.1002/cncr.21378

PMID:16116604

Abstract

BACKGROUND

The p16INK4a gene product is overexpressed strongly in abnormal cervical epithelia and may serve as a valuable biomarker to identify abnormal cells in cervical smears or liquid-based cytology samples.

METHODS

The authors performed p16INK4a immunocytochemistry to locate cells that expressed p16INK4a in liquid-based cytology samples and used a nuclear scoring system based on several morphologic criteria to interpret the degree of abnormality of these cells.

RESULTS

Among 108 samples that were scored as normal in Papanicolaou-stained, parallel slides, any p16INK4a-positive cells were observed in 13 samples (12%), but only 1 of 108 samples (1%) was scored abnormal after applying nuclear scoring criteria. In the group of 52 low-grade squamous intraepithelial lesion (LSIL) samples, 19 samples (37%) were positive for any p16INK4a reactivity, but only 5 of those samples (10%) were scored abnormal after applying the nuclear score. Among the 50 high-grade squamous intraepithelial lesion (HSIL) samples, 49 samples (98%) were positive for p16INK4a and were scored as abnormal. Comparison of the scoring results of independent observers revealed good reproducibility of the nuclear score.

CONCLUSIONS

The current results suggested that p16INK4a enables the location of potentially abnormal cells on liquid-based cytology samples. The nuclear score facilitated interpretation of the degree of abnormality of p16INK4a-stained cells. Thus, locating potentially abnormal cells by p16INK4a immunocytochemistry and their interpretation based on the nuclear score described here may help to identify patients with HSIL in cytologic screening programs and may represent a new approach for reducing the number of equivocal or misinterpreted cytologic specimens.

摘要

背景

p16INK4a基因产物在异常宫颈上皮中强烈过表达，可作为一种有价值的生物标志物，用于识别宫颈涂片或液基细胞学样本中的异常细胞。

方法

作者进行p16INK4a免疫细胞化学检测，以定位液基细胞学样本中表达p16INK4a的细胞，并使用基于多种形态学标准的核评分系统来解释这些细胞的异常程度。

结果

在巴氏染色并行玻片检查中被评为正常的108份样本中，13份样本（12%）观察到有p16INK4a阳性细胞，但应用核评分标准后，108份样本中只有1份（1%）被评为异常。在52份低级别鳞状上皮内病变（LSIL）样本组中，19份样本（37%）有任何p16INK4a反应性阳性，但应用核评分后，这些样本中只有5份（10%）被评为异常。在50份高级别鳞状上皮内病变（HSIL）样本中，49份样本（98%）p16INK4a阳性并被评为异常。独立观察者评分结果的比较显示核评分具有良好的可重复性。

结论

目前的结果表明，p16INK4a能够在液基细胞学样本上定位潜在的异常细胞。核评分有助于解释p16INK4a染色细胞的异常程度。因此，通过p16INK4a免疫细胞化学定位潜在的异常细胞并基于本文所述的核评分进行解读，可能有助于在细胞学筛查项目中识别HSIL患者，并可能代表一种减少可疑或解读错误的细胞学标本数量的新方法。