[403] ProEx C as an Adjunct Molecular Marker To Improve the Detection of Urothelial Carcinoma

Neda A Moatamed, Serge Alexanian, Jian Yu Rao, Mellisa Cobarrubias, Mary Levin, Gretchen Galliano, Sophia K Apple. David Geffen School of Medicine at UCLA, Los Angeles, CA

Background: ProEx C is a novel antibody targeting the expression of topoisomerase II-alpha and minichromosome maintenance protein-2. Both proteins are overexpressed in the cell nucleus during aberrant S-phase induction of the neoplastic and HPV infected cells. Other studies have demonstrated ProEx C as an adjunct marker for assessing dysplasia in gynecologic specimens especially in the cervical biopsies and smears. A significant number of urine cytology specimens are diagnosed as “atypical” that triggers additional procedures that may result in patient discomfort and/or increase in cost. This study was designed to determine the utility of ProEx C in urine cytology samples for improving the detection of urothelial carcinoma.
Design: Sixty urine cytology specimens (12 negative, 35 atypical, and 13 positive cases) from July 2010-June 2011 which had a surgical follow up were retrieved. Residual fluid from the liquid-based ThinPrep urine specimen was used to make an additional slide for immunohistochemical stain. Smears were screened to confirm adequacy and cytologic diagnosis. ProEx C was recorded as positive in cytology samples when nuclear staining was seen in morphologically atypical urothelial cells and as negative if no staining was observed.
Results: A positive ProEx C stain had a sensitivity of 78.4%, specificity of 87%, PPV of 90.6% and NPV of 71.48% for the detection of urothelial carcinoma. Using McNemar-Fisher exact Chi-square analysis in a 2x2 table, a P-value of 0.016 was obtained when the ProEx C positive and negative stains compared in positive and negative follow ups in the cases diagnosed as “atypical” in Tables 1 & 2.

Table 1. Results of ProEx C stain in urine cytology specimen
StainCytology Diagnoses (n=60)
 Negative (n=12)Atypical (n=35)Positive (n=13)
ProEx C +02012
ProEx C -12121

Table 2. Results of ProEx C staining with follow-up diagnoses (n=60)
StainNegative cytology (n=12)Atypical cytology (n=35) Chi-Sq P-value = 0.016Positive cytology (n=13)
 Negative follow-upPositive follow-upNegative follow-upPositive follow-upNegative follow-upPositive follow-up
ProEx C+00317012
ProEx C-1208701

Conclusions: Based on this study, as outlined in the tables, ProEx C stain can be a useful adjunct test to urine cytology even with limited specimens. Significant difference was seen for positive Proex-C stain in atypical cases having a positive follow up versus negative follow up. Therefore, this test may assist in further classification of “indeterminate” or “atypical” diagnoses in urine smears.
Category: Cytopathology

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 72, Tuesday Morning


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