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

✍ Scribed by Kelly, Deidra ;Kincaid, Erik ;Fansler, Zoya ;Rosenthal, Dorothy L. ;Clark, Douglas P.

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 135 KB
• Volume: 108
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/cncr.22288

✦ Synopsis

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 TM 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 TM 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 TM 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 TM C assay was validated successfully in the authors' cytology laboratory. Using biopsy-proven HSIL as an endpoint, the ProEx TM 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 TM C sensitivity for biopsy-proven HSIL was 70.6% greater than HSILþ cytology (50% vs. 85.3%).

ProEx TM C also showed a 114% increase in PPV relative to ASC-US cytology (21.1% vs. 44.6%).

CONCLUSIONS. The ProEx TM C immunocytochemical assay can be integrated into a clinical cytology laboratory and may increase the PPV of LBC for biopsy-proven