Validation of a novel immunocytochemical assay for topoisomerase II-α and minichromosome maintenance protein 2 expression in cervical cytology

Authors

  • Kenneth R. Shroyer MD, PhD,

    Corresponding author
    1. Department of Pathology, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado
    • Department of Pathology, University of Colorado at Denver and Health Sciences Center, Mail Stop 8104, P.O. Box 6511, 12800 East 19th Avenue, Aurora, CO 80045
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    • Fax: (303) 724-3712

    • Dr. Shroyer is a member of the TriPath Oncology Scientific Advisory Board and has previously received honoraria from TriPath, but not related to the preparation of this or any other article.

  • Petra Homer,

    1. Department of Pathology, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado
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  • David Heinz,

    1. Department of Pathology, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado
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  • Meenakshi Singh MD

    1. Department of Pathology, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado
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Abstract

BACKGROUND.

Cervical cytopathology has limited specificity for the detection of underlying clinically significant lesions in cases with low-grade cytologic abnormalities. The current study evaluated the performance of a novel immunocytochemical test (ProEx C) for topoisomerase II alpha (TOP2A) and minichromosome maintenance protein 2 (MCM2) in normal versus high-grade squamous intraepithelial lesion (HSIL) and positive control (SiHa) pooled cytology preparations and in a pilot series of prospectively collected patient specimens.

METHODS

TOP2a and MCM2 were detected as markers of aberrant S-phase induction in SurePath cervical cytology specimens by an indirect polymer-based immunoperoxidase method (ProEx C, TriPath Oncology, Burlington, NC). Slides were scored based on specimen adequacy, the presence of nuclear stain in epithelial cells, and the association of nuclear staining with cytologic atypia (≥atypical squamous cell of undetermined significance [ASC-US] or atypical glandular cells [AGC]).

RESULTS

Intense nuclear staining was detected in cytologically abnormal cells but not in most normal squamous and glandular cells. Slides were scored positive in pooled samples in 1 of 40 (2.5%) cases that were negative for intraepithelial neoplasia or malignancy (NIL), in 40 of 40 (100%) SiHa-spiked NIL, and in 40 of 40 (100%) HSILs. There was 100% concordance in test classification of 20 slides between 2 pathologists. Subsequent evaluation of prospectively collected patient specimens was positive for ProEx C in none of 10 NIL (0%), 2 of 10 ASC-US (20%), 5 of 10 low-grade SIL (LSIL) (50%), and in 10 of 10 (100%) HSILs.

CONCLUSIONS

The ProEx C test showed almost no variability with regard to scoring and staining reproducibility and was consistently positive in HSIL. Further studies are indicated to evaluate the potential role of ProEx C as a diagnostic adjunct for the triage of ASC-US/LSIL. Cancer (Cancer Cytopathol) 2006;108:. © 2006 American Cancer Society.

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