ProEx C immunocytochemistry and high-risk human papillomavirus DNA testing in papanicolaou tests with atypical squamous cell (ASC-US) cytology: correlation study with histologic biopsy.
BACKGROUND
Papanicolaou tests with atypical squamous cells of undetermined significance (ASC-US) cytology and adjunct testing for high-risk human papillomaviruses (hr-HPV) are helpful in detecting high-grade disease. Detection of disease may be further improved with molecular markers known to be overexpressed in cervical carcinoma. ProEx C detects 2 such molecular markers, minichromosome maintenance protein 2 and topoisomerase II, which are associated with abnormal cell cycle regulation.


OBJECTIVE
To determine the utility of ProEx C as a marker for high-grade cervical intraepithelial neoplasia 2+ disease when compared with hr-HPV status in Papanicolaou tests with ASC-US cytology.


METHODS
A SurePath slide was prepared on all ASC-US cases from the residual SurePath vial pellet and stained using the ProEx C reagent prediluted with water-bath antigen retrieval, using a Dako autostainer. Nuclear staining of cytologically atypical squamous cells was considered a positive result. Adjunct testing for hr-HPV used Digene Hybrid Capture 2. Follow-up biopsy results were available for review following the Papanicolaou test.


RESULTS
Two hundred patients with ASC-US diagnoses were part of this study. The sensitivities of ProEx C and hr-HPV testing in detecting high-grade cervical intraepithelial neoplasia 2+ disease were 98.04% and 82.35%, respectively, whereas the specificity for detecting high-grade disease was 74.50% and 73.15%, respectively.


CONCLUSIONS
ProEx C staining is a more sensitive and specific biomarker for detecting cervical disease than adjunct testing for hr-HPV status in Papanicolaou tests with ASC-US.
Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, Georgia 30322, USA. Momin.siddiqui@emoryhealthcare.org
Momin T
MT
Siddiqui
Kelly
K
Hornaman
Cynthia
C
Cohen
Aziza
A
Nassar
D000293:Adolescent; D000328:Adult; D052685:Alphapapillomavirus / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002584:Cervix Uteri / Q000378:metabolism* / Q000473:pathology*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008875:Middle Aged; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000378:metabolism; D065006:Papanicolaou Test; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D014626:Vaginal Smears / Q000379:methods*
D000951:Antigens, Neoplasm; D015415:Biomarkers; D018797:Cell Cycle Proteins; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2; D004250:DNA Topoisomerases, Type II