Yoshida Tomomi, Fukuda Toshio, Sano Takaaki, Kanuma Tatsuya, Owada Nobuo, Nakajima Takashi
Department of Tumor Pathology, Gunma University Graduate School of Medicine, Gunma, Japan.
Cancer. 2004 Apr 25;102(2):100-8. doi: 10.1002/cncr.20046.
In cervical lesions, the overexpression of p16 is reported to be closely associated with high-risk human papillomavirus (HPV) infection. The objective of the current study was to confirm the usefulness of liquid-based cervical specimens for p16 staining as well as tissue sections.
A total of 98 patients with cervical lesions were entered into the current study. After the cytologic examination using liquid-based cervical smears, the same slides were immunostained for p16 and were compared with slides of simultaneously obtained, immunohistologically stained tissue sections. Moreover, the status of the HPV infection was examined by polymerase chain reaction using residual cytologic samples.
Using liquid-based Pap smears, 98 cases were diagnosed as atypical squamous cells of undetermined significance (38 cases), low-grade squamous intraepithelial lesion (12 cases), high-grade squamous intraepithelial lesion (HSIL) (33 cases), and invasive carcinoma (15 cases). The concordance rate between the cytologic and histologic diagnoses was found to be higher in high-grade lesions compared with low-grade lesions. Immunohistochemistry revealed that all HSIL and invasive carcinoma cases contained p16-positive cells in the liquid-based Pap smears and diffuse p16 staining was observed in all high-grade lesions with greater than CIN Grade 3 cervical intraepithelial neoplasia except for two adenocarcinoma cases. Of the 98 cases, 60 were found to be positive for high-risk HPV and 55 of these 60 HPV-positive cases were found to be p16 positive on cytologic examination. There were 16 cases that demonstrated marked discrepancies between the cytologic and histologic diagnoses.
The results of the current study confirmed that the immunohistochemical detection of p16 was more sensitive and specific than HPV status in cervical lesions using a liquid-based method as well as tissue samples, suggesting that p16 should be used as a satisfactory biomarker for the primary screening of cervical cytology.
在宫颈病变中，据报道p16的过表达与高危型人乳头瘤病毒（HPV）感染密切相关。本研究的目的是证实液基宫颈标本用于p16染色以及组织切片的实用性。
共有98例宫颈病变患者纳入本研究。使用液基宫颈涂片进行细胞学检查后，对同一张玻片进行p16免疫染色，并与同时获取的免疫组织化学染色组织切片玻片进行比较。此外，使用剩余的细胞学样本通过聚合酶链反应检测HPV感染状况。
使用液基巴氏涂片，98例被诊断为意义不明确的非典型鳞状细胞（38例）、低级别鳞状上皮内病变（12例）、高级别鳞状上皮内病变（HSIL）（33例）和浸润癌（15例）。发现高级别病变的细胞学和组织学诊断符合率高于低级别病变。免疫组织化学显示，所有HSIL和浸润癌病例的液基巴氏涂片中均含有p16阳性细胞，除两例腺癌病例外，所有CIN 3级以上的高级别病变中均观察到弥漫性p16染色。在98例病例中，60例高危型HPV检测呈阳性，其中55例HPV阳性病例的细胞学检查显示p16阳性。有16例病例的细胞学和组织学诊断存在明显差异。
本研究结果证实，使用液基方法以及组织样本时，在宫颈病变中p16的免疫组织化学检测比HPV状态更敏感和特异，提示p16应用作宫颈细胞学初筛的理想生物标志物。
