Kelly Deidra, Kincaid Erik, Fansler Zoya, Rosenthal Dorothy L, Clark Douglas P
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21287-6940, USA.
Cancer. 2006 Dec 25;108(6):494-500. doi: 10.1002/cncr.22288.
Routine liquid-based cytology (LBC) provides excellent sensitivity for the detection of cervical high-grade squamous intraepithelial lesion (HSIL); however, its specificity is low. Consequently, many women who have atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL) cytology undergo unnecessary colposcopy. The authors hypothesized that a novel immunocytochemical assay (ProEx C) that can be performed on LBC slides had a significantly higher positive predictive value (PPV) for biopsy-proven HSIL compared with routine LBC.
The ProEx C immunocytochemical assay utilizes a cocktail of monoclonal antibodies directed against proteins associated with aberrant S-phase cell cycle induction (topoisomerase IIA, minichromosome maintenance protein 2). The ProEx C reagents were validated in the authors' laboratory for staining and scoring reproducibility, open-vial stability, and accuracy before a retrospective analysis using these reagents was performed on 317 residual cytology samples. Sensitivity, specificity, PPV, and negative predictive value (NPV) for the detection of biopsy-proven HSIL were determined.
The ProEx C assay was validated successfully in the authors' cytology laboratory. Using biopsy-proven HSIL as an endpoint, the ProEx C assay yielded a sensitivity of 85.3%, specificity of 71.7%, PPV of 44.6%, and NPV of 94.8%. Compared with the routine LBC results in the same cohort, the ProEx C sensitivity for biopsy-proven HSIL was 70.6% greater than HSIL+ cytology (50% vs. 85.3%). ProEx C also showed a 114% increase in PPV relative to ASC-US cytology (21.1% vs. 44.6%).
The ProEx C immunocytochemical assay can be integrated into a clinical cytology laboratory and may increase the PPV of LBC for biopsy-proven HSIL.
常规液基细胞学检查（LBC）对检测宫颈高级别鳞状上皮内病变（HSIL）具有出色的敏感性；然而，其特异性较低。因此，许多细胞学检查结果为意义不明确的非典型鳞状细胞（ASC-US）或低级别鳞状上皮内病变（LSIL）的女性接受了不必要的阴道镜检查。作者推测，一种可在LBC玻片上进行的新型免疫细胞化学检测方法（ProEx C）与常规LBC相比，对经活检证实的HSIL具有显著更高的阳性预测值（PPV）。
ProEx C免疫细胞化学检测方法使用了一种针对与异常S期细胞周期诱导相关蛋白质（拓扑异构酶IIA、微小染色体维持蛋白2）的单克隆抗体混合物。在对317份剩余细胞学样本进行回顾性分析之前，ProEx C试剂在作者的实验室中进行了染色和评分重现性、开瓶稳定性及准确性的验证。确定了检测经活检证实的HSIL的敏感性、特异性、PPV和阴性预测值（NPV）。
ProEx C检测方法在作者的细胞学实验室中成功得到验证。以经活检证实的HSIL为终点，ProEx C检测方法的敏感性为85.3%，特异性为71.7%，PPV为44.6%，NPV为94.8%。与同一队列中的常规LBC结果相比，ProEx C对经活检证实的HSIL的敏感性比HSIL+细胞学检查结果高70.6%（50%对85.3%）。ProEx C相对于ASC-US细胞学检查结果的PPV也提高了114%（21.1%对44.6%）。
ProEx C免疫细胞化学检测方法可整合到临床细胞学实验室中，可能会提高LBC对经活检证实的HSIL的PPV。
