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Diagn Cytopathol. 2015 Mar;43(3):181-7. doi: 10.1002/dc.23193. Epub 2014 Jun 28.

Expression of ProEx C in primary and metastatic urothelial carcinoma.

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Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.



ProEx C is an antibody cocktail targeting the expression of topoisomerase IIα and minichromosome maintenance protein-2. Both these proteins are over-expressed in the cell nucleus during aberrant S-phase induction of neoplastic cells, which leads to cell proliferation. The aim of this study was to determine whether ProEx C expression can detect primary and metastatic urothelial carcinoma (UC).


Thirty one fine needle aspiration cell blocks (CB) with metastatic UC were identified. Immunohistochemical staining for ProEx C and thrombomodulin was performed. Additionally, staining for Pro Ex C was also performed in tissue microarrays (TMA) of 46 cases of primary UC and carcinomas from colon (80), stomach (31), pancreas (33), liver (92), ovary (24), endometrium (25), breast (60), lung (27), kidney (32), and prostate (44), as well as melanoma (22). Nuclear staining of ProEx C and membrane staining of thrombomodulin in at least 10% tumor cells was considered a positive result.


Both ProEx C and thrombomodulin have similar sensitivity for metastatic UC (84% vs. 77%, p=0.75; whereas ProEx C yielded a higher sensitivity of 93% for primary UC than thrombomodulin (72%, p=0.01). In addition to UC, ProEx C is also expressed in most of the malignant neoplasms tested in our TMA study, and has the highest sensitivity in colon and stomach carcinomas (94%).


ProEx C has high sensitivity for UC. However, it is also expressed in carcinomas of colon, stomach, breast, and lung carcinomas and may not be a useful marker for workup of metastatic UC.


ProEx C; thrombomodulin; tissue microarray; urine; urothelial carcinoma

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