ProEx C as an adjunct marker to improve cytological detection of urothelial carcinoma in urinary specimens.
BACKGROUND
ProEx C is an antibody cocktail targeting the expression of topoisomerase IIα and minichromosome maintenance protein-2. ProEx C staining is being used to assist in diagnoses of the gynecological specimens. This study was designed to determine the utility of ProEx C in urine cytology samples for improving the detection of urothelial carcinomas where a significant number of urine cytology specimens are diagnosed as "atypia."


METHODS
Sixty urinary specimens (12 negative, 13 positive, and 35 atypical cases) were stained with ProEx C, and ProEx C results were recorded as positive when nuclear staining was only seen in at least one morphologically atypical urothelial cell.


RESULTS
All 12 benign cytology samples showed negative staining with ProEx C. Twelve of 13 cases that had a malignant cytologic diagnosis showed a positive nuclear staining of the malignant cells. Eighteen of 35 cases with atypical cytologic diagnoses showed positive nuclear staining. Of the 35 cases with "atypia," 17 had a malignant histopathologic follow-up. In this study, ProEx C stain had an overall sensitivity of 78.4%, specificity of 95.7%%, positive predictive value of 96.7%, and negative predictive value of 73.3% for the detection of urothelial carcinoma.


CONCLUSIONS
ProEx C stain is a useful adjunct test to urine cytologic analysis, even in specimens with limited cellularity. In urinary smears, this test is most useful in stratification of the "atypical" diagnoses into benign and malignant subsets. To the authors' knowledge, this is the first study of ProEx C application in urine cytology as an adjunct marker for detection of urothelial carcinoma.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, California 90095-1732, USA. nmoatamed@mednet.ucla.edu
Neda A
NA
Moatamed
Jian-Yu
JY
Rao
Serge
S
Alexanian
Melissa
M
Cobarrubias
Mary
M
Levin
David
D
Lu
Sophia K
SK
Apple
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000652:urine; D018797:Cell Cycle Proteins / Q000032:analysis* / Q000276:immunology; D003581:Cytodiagnosis; D004250:DNA Topoisomerases, Type II / Q000032:analysis* / Q000276:immunology; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D064111:Minichromosome Maintenance Complex Component 2; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000032:analysis* / Q000276:immunology; D011379:Prognosis; D014556:Urine / Q000166:cytology*; D014571:Urologic Neoplasms / Q000175:diagnosis* / Q000652:urine; D014626:Vaginal Smears; D055815:Young Adult
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2; D004250:DNA Topoisomerases, Type II