Proviral Integration Site Moloney Murine Leukemia Virus (PIM) Expression in Urothelial Carcinoma
Daniel J Albertson, Jared J Bearss, David J Bearss, Sheryl Tripp, Ting Liu. University of Utah, Salt Lake City, UT; Huntsman Cancer Institute, Salt Lake City, UT; ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT; Brigham Young University, Provo, UT
Background: The Proviral integration site Moloney murine leukemia virus (PIM) family is a group of proteins belonging to the calcium dependent protein kinases with serine/threonine kinase activity. Many studies have demonstrated overexpression of this family in hematologic and epithelial malignancies. The aim of the investigation was to evaluate PIM expression (PIM-1, 2, 3) in urothelial carcinoma and to assess for expression that may contribute to disease progression and serve as a site for PIM kinase targeted therapy.
Design: Seventy-two cases of urothelial carcinoma were included in this retrospective study of surgical biopsy and resection specimens from the University of Utah Department of Pathology (retrieved from 2008-2011). Tissue was stained with commercially available antibodies against PIM-1, PIM-2, and PIM-3. Cases were divided into three groups (invasive high grade urothelial carcinoma (n=49), non-invasive high grade urothelial carcinoma/carcinoma in situ (n=16), and non-invasive low grade urothelial carcinoma (n=7)). Individual cases were then given a score (0-4) based upon a percentage of cells staining positive for each antibody (<5%=0; 5-25%=1; 26-50%=2; 51-75%=3; >75%=4). A score of 2 or greater was considered a positive finding.
Results: Increased PIM-1, PIM-2 and PIM-3 expression was seen in a significant number of urothelial carcinoma cases when compared to adjacent bladder tissue.
|low grade non-invasive urothelial carcinoma||29%(2/7)||43%(3/7)||86%(6/7)|
|high grade non-invasive urothelial carcinoma||44%(7/16)||50%(8/16)||44%(7/16)|
|high grade invasive urothelial carcinoma||10%(5/49)||27%(13/49)||18%(9/49)|