Longitudinal clinical evaluation of a novel antibody cocktail for detection of high-grade squamous intraepithelial lesions on cervical cytology specimens

Arch Pathol Lab Med. 2008 Jun;132(6):918-25. doi: 10.5858/2008-132-918-LCEOAN.

Abstract

Context: Although cervical cancer screening by cytology is successful, the test continues to show relatively poor operating characteristics. Cell cycle markers may enhance detection of high-grade squamous intraepithelial lesions.

Objective: To determine the clinical usefulness of ProExC, an immunocytochemical assay for cell cycle components, performed on routine cervical cytology samples.

Design: Cervical cytology samples were collected using the SurePath method. Residual cells remaining after preparation of the Papanicolaou-stained slide were used to make a second slide for ProExC staining using an indirect polymer-based immunoperoxidase method. Only adequately cellular slides were evaluated for the presence of nuclear staining within cytologically abnormal epithelial cells. Results were correlated with clinical follow-up.

Results: Six hundred twenty-four samples were satisfactorily cellular and stained. Correlation with clinical follow-up for subsequent cervical intraepithelial neoplasia 2+ on biopsy/high-grade squamous intraepithelial lesion on cytology (CIN 2+/HSIL) showed that 434 results were true negative, 78 true positive, 18 false-negative, and 94 false-positive, resulting in a sensitivity/specificity of 81%/82%. When ProExC results were combined with any level of cytologic atypia, sensitivity for CIN 2+/HSIL was 92% and specificity was 84%.

Conclusions: ProExC shows promise as an aid in enhancing the sensitivity and specificity of cervical cytology for subsequent CIN 2+/HSIL and may be useful in identifying those cervical lesions most apt to progress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies*
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / virology
  • Cell Cycle Proteins / immunology
  • Cell Cycle Proteins / metabolism
  • DNA Topoisomerases, Type II / immunology
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • False Negative Reactions
  • False Positive Reactions
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Longitudinal Studies
  • Minichromosome Maintenance Complex Component 2
  • Nuclear Proteins / immunology
  • Nuclear Proteins / metabolism
  • Papanicolaou Test
  • Papillomavirus Infections / epidemiology
  • Sensitivity and Specificity
  • Uterine Cervical Dysplasia / diagnosis*
  • Uterine Cervical Dysplasia / metabolism
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears

Substances

  • Antibodies
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • MCM2 protein, human
  • Minichromosome Maintenance Complex Component 2
  • DNA Topoisomerases, Type II