ProExC as an adjunct marker to improve cytological detection of urothelial carcinoma in urinary specimens

Abstract

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. Cancer (Cancer Cytopathol) 2013;121:320–8. © 2013 American Cancer Society.

Comparative Evaluation of ProEx C and ImmunoCyt/uCyt Assays in Atypical Urine Cytology

“…22 In particular, by segregating LGUC cases from HGUC cases, as we did in this report, ProEx C displayed a lower sensitivity in detecting LGUC (72%; Table 6) than in detecting HGUC (92%, Table 7), as alluded to in the previous publication. 22 A recently published study, 32 using histologic sections of the urothelial neoplasia, has demonstrated that the ProEx C staining involves the full thickness of the cancerous epithelium in HGUC, whereas the reaction is focal in LGUC and the positive cells may not reach the surface for exfoliation into the urine samples. This observation may account for the lower sensitivity of the assay in LGUC.…”

“…ProEx C scoring was recorded as positive if at least one morphologically AUC displayed positive nuclear staining. This protocol was also performed in the publication by Moatamed et al 22 Examples of the ProEx C stains of AUCs and their corresponding hematoxylin-eosin-stained histologic images of low-grade papillary urothelial carcinoma (LGUC; Figure 2 …”

“…The first published study 22 using ProEx C in urinary cytology presented quite favorable test characteristics for ProEx C in defining definitive benign and malignant cytologic specimens for predicting both LGUC and HGUC. In particular, the study showed that ProEx C was most useful in stratifying the diagnosis when the cytology was nondefinitive (ie, AUC).…”

“…[19][20][21] Recently, the utility of the ProEx C antibody cocktail in urinary cytology as an ancillary test to aid in the stratification of AUCs was introduced. 22 That antibody cocktail targeted MCM2 and TOP2A, markers that are highly expressed in hyperactive basal/parabasal cells, as well as in cancer cells during the aberrant induction of S phase. 9,23 The current study was designed to compare uCyt, one of the widely used ancillary tests at our institution, to the utility of ProEx C in atypical urinary cytology.…”

ProEx C as Diagnostic Marker for Detection of Urothelial Carcinoma in Urinary Samples: A Review

“…Besides, these tests are time-consuming and more costly to perform 54. The first published study using ProEx C in urinary cytology 55 showed that ProEx C was very useful in stratifying patients with diagnosis of atypical urothelial cells into benign and malignant subsets. In a follow-up comparative study, ProEx C showed a high sensitivity in detecting HGUC (92%) (Figure 1A) and a low sensitivity in LGUC (72%) (Figure 1B).…”