Ling Jian, Wiederkehr Urs, Cabiness Spring, Shroyer Kenneth R, Robinson J Paul
Medical System Department, Automation and Data System Division, Southwest Research Institute, 6220 Culebra Road, San Antonio, TX 78238, USA.
Diagn Cytopathol. 2008 Feb;36(2):76-84. doi: 10.1002/dc.20763.
The Pap test used for cervical cancer screening is subjective, labor-intensive, and has relatively low sensitivity and specificity for the detection of underlying clinically significant lesions. The objective of this study is to develop a biomarker/flow cytometry-based approach for cervical cancer screening. Immunofluorescence technology to quantify cervical cell expression of two biomarkers p16(INK4A) and Mcm5 was developed and evaluated by both microscopy and flow cytometry. The capability of using biomarker/flow cytometry approach to detect rare-event dysplastic cells in a large background of benign epithelial and inflammatory cells was evaluated. The results indicate that flow cytometry could detect 0.01% dysplastic cells in a background of normal cervical epithelial cells with the combination of the two biomarkers. Thirty-two clinical specimens were used to test the biomarker/flow cytometry-based approach and the results were compared with the liquid-based cervical cytology. The experiment yielded 100% sensitivity and 93% specificity with reference to the liquid-based cervical cytology. This study indicates the promise of using multi-color fluorescence flow cytometry for biomarker-based cervical cancer screening. This molecular-based, potentially high-throughput and automated method is expected to provide an alternative/auxiliary means of cervical cancer screening.
用于宫颈癌筛查的巴氏试验主观性强、劳动强度大,且对潜在临床显著病变的检测灵敏度和特异性相对较低。本研究的目的是开发一种基于生物标志物/流式细胞术的宫颈癌筛查方法。通过显微镜和流式细胞术开发并评估了用于定量宫颈细胞中两种生物标志物p16(INK4A)和Mcm5表达的免疫荧光技术。评估了使用生物标志物/流式细胞术方法在大量良性上皮细胞和炎性细胞背景中检测罕见的发育异常细胞的能力。结果表明,结合两种生物标志物,流式细胞术能够在正常宫颈上皮细胞背景中检测出0.01%的发育异常细胞。使用32份临床标本对基于生物标志物/流式细胞术的方法进行测试,并将结果与液基宫颈细胞学检查结果进行比较。相对于液基宫颈细胞学检查,该实验的灵敏度为100%,特异性为93%。本研究表明了使用多色荧光流式细胞术进行基于生物标志物的宫颈癌筛查的前景。这种基于分子的、潜在的高通量和自动化方法有望提供一种宫颈癌筛查的替代/辅助手段。