The Combination of ProEx C and uCyt Tests Improve Detection of Urothelial Carcinoma in Atypical Urine Samples
Maria E Vergara-Lluri, Eugenia Hu, Mary Levin, Jianyu Rao, Sophia K Apple, Neda A Moatamed. David Geffen School of Medicine at UCLA, Los Angeles, CA
Background: Detection of urothelial cell carcinoma (UCC) by urine cytology can be challenging, especially for low grade tumors, and adjunctive markers, such as ImmunoCyt (uCyt), are useful. Recently, we found that ProEx C may be an additional molecular marker to improve detection of UCC. ProEx C, originally developed for assessing dysplasia in gynecologic specimens, is an assay targeting expression of topoisomerase II-α & minichromosome maintenance protein-2. The current study evaluated the utility of ProEx C combined with uCyt as adjunct markers in urine cytology.
Design: A retrospective study consisting of a total of 71 patients with the diagnosis of urothelial cell atypia was performed, all of which had prior uCyt tested. Archived ThinPrep slides were restained with ProEx C immunoassay. ProEx C was recorded as positive when nuclear staining was seen in atypical urothelial cells. uCyt was considered positive if >5 cells were seen to fluoresce green or red. All cases had follow-up surgical biopsy (13 negative, 18 low grade UCC, 37 high grade UCC).
Results: When ProEx C and uCyt were performed individually, each had an 84% positive rate for high grade UCC. Although ProEx C had a slightly low positive rate in low grade UCC compared to uCyt (72% versus 83%), the positive rate for ProEx C vs uCyt in the negative follow-up group was also slightly low (i.e. false positive rate, 38% versus 54%). The combination of the two tests in an 'either/or' setting detected 17 out of 18 (94%) low grade tumors and 34 of 37 (92%) high grade tumors (p=0.06 and p=0.02, respectively, compared to negative group); however, 8 of 13 (62%) negative cases were positive for ProEx C or uCyt.
|TEST||Staining Results||Negative, n=13 (%)||Low Grade, n=18 (%)||High Grade, n=37 (%)||Combined Low & High Grade, n=55 (%)|
|ProEx C||+||5 (38)||13 (72)*||31 (84)**||44 (80)**|
|-||8 (62)||5 (28)||6 (16)||11 (20)|
|uCyt||+||7 (54)||15 (83)||31 (84)||46 (84)**|
|-||6 (46)||3 (17)||6 (16)||9 (16)|
|ProEx C/uCyt||+||8 (62)||17 (94)*||34 (92)**||51 (93)**|
|-||5 (38)||1 (6)||3 (8)||4 (7)|