Patterns and Significance of PIM Kinases in Urothelial Carcinoma.

Abstract

The Provirus integrating site Moloney murine leukemia virus (Pim) family are proteins with serine/threonine kinase activity. Studies have demonstrated overexpression of Pims in cancer. To our knowledge, only a single study has examined Pim-1 in urothelial carcinoma. The aim of this investigation was to evaluate Pim-1, Pim-2, and Pim-3 in urothelial carcinoma and assess for expression that may contribute to disease progression and serve as a site for targeted therapy. This retrospective study included 137 cases taken from specimens from the University of Utah, Department of Pathology (2008 to 2011). Tissue was stained with antibodies against Pim-1, Pim-2, and Pim-3. Cases were classified into 3 groups, based upon current World Health Organization criteria (invasive high-grade urothelial carcinoma [IHG] [n=84], noninvasive high-grade urothelial carcinoma/carcinoma in situ [n=32], and noninvasive low-grade urothelial carcinoma [NILG] [n=21]). Cases were scored and recorded as positive or negative on the basis of the percentage of cells with cytoplasmic and/or nuclear staining. NILG showed higher expression of Pim-1 (relative expression rate [RER]=2.28; 95% confidence interval [CI], 0.183-0.764) and Pim-3 (RER=3.06; 95% CI, 0.423-0.816) compared with other lesions. IHG had lower expression of Pim-1 (RER=0.31; 95% CI, 0.401-0.844) and Pim-3 (RER=0.354; 95% CI, 0.322-0.816) and noninvasive high-grade urothelial carcinoma (NIHG) demonstrated increased expression of Pim-1 and (RER=2.09; 95% CI, 0.124-0.739) and Pim-2 (RER=1.70; 95% CI, 0.151-0.591). At least 1 Pim kinase protein was expressed at the following rates: 49% in IHG, 66% in NIHG, and 76% in NILG. A high percentage of urothelial carcinomas express Pim kinases. Pim expression differs in NILG, NIHG, and IHG lesions.