Detection of cervical high‐grade squamous intraepithelial lesions from cytologic samples using a novel immunocytochemical assay (ProEx™ C)

• Published in: Cancer 2006-12, Vol.108 (6), p.494-500
• Main Authors: Kelly, Deidra, Kincaid, Erik, Fansler, Zoya, Rosenthal, Dorothy L., Clark, Douglas P.
• Format: Article
• Language: English
• Subjects: Algorithms; Antigens, Neoplasm - metabolism; Biological and medical sciences; Biological Assay; Cell Cycle Proteins - metabolism; cervical cytology; Cervical Intraepithelial Neoplasia - diagnosis; Cervical Intraepithelial Neoplasia - metabolism; DNA Topoisomerases, Type II - metabolism; DNA-Binding Proteins - metabolism; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; high‐grade squamous intraepithelial lesion; Humans; immunocytochemistry; liquid‐based cytology; Medical sciences; Minichromosome Maintenance Complex Component 2; Neoplasms, Squamous Cell - diagnosis; Neoplasms, Squamous Cell - metabolism; Nuclear Proteins - metabolism; Predictive Value of Tests; Retrospective Studies; Sensitivity and Specificity; Tumors; Uterine Cervical Neoplasms - diagnosis; Uterine Cervical Neoplasms - metabolism; Vaginal Smears
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.22288

BACKGROUND. 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. METHODS. 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. RESULTS. 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%). CONCLUSIONS. The ProEx™ C immunocytochemical assay can be integrated into a clinical cytology laboratory and may increase the PPV of LBC for biopsy‐proven HSIL. Cancer (Cancer Cytopathol) 2006. © 2006 American Cancer Society. Routine liquid‐based cytology (LBC) provides excellent sensitivity for the detection of cervical high‐grade squamous epithelial lesion (HSIL); however, its specificity is low. In the current study, the authors determined that the ProEx™ C immunocytochemical assay may increase the positive predictive value of LBC for biopsy‐proven HSIL.