Abstract 4667: Elevated expression of the stress oncoprotein LEDGF/p75 in major human cancers

Abstract

Abstract Long-term cumulative exposure to environmental factors (i.e., dietary habits, unhealthy lifestyle, infectious agents, etc) lead to chronic inflammation and an augmented state of cellular oxidative stress, which contribute to the etiology and progression of various human cancers. We reported previously that lens epithelium derived growth factor p75 (LEDGF/p75), a transcription coactivator, has an elevated expression in human prostate tumors and cell lines. We hypothesize that LEDGF/p75 might be highly expressed in tissues with elevated oxidative stress such as tumors, because of its ability to transcriptionally activate stress genes that promote resistance to stress- and chemotherapy-induced cell death. To date, there have not been any comprehensive studies aimed at investigating the expression of LEDGF/p75 in human cancers. We performed an expression analysis of LEDGF/p75 protein in a panel of human cancers using immunohistochemistry on commercially available tissue microarrays (TMAs). Paraffin embedded tissue specimens were deparaffinized, rehydrated and stained with either a rabbit anti-LEDGF/p75 serum or the rabbit pre-immune serum as an antibody control, using a Biogenic i6000 auto stainer (Biogenex Corp.). Images were acquired using an Olympus BX50 microscope equipped with a Spot RT3TM camera. The TMA slides were assessed for LEDGF/p75 immunoreactivity by a pathologist who was blinded for the tumor/normal status of the tissues. A 4-tier grading system (0-negative, 1-weak, 2-moderate and 3-strong staining intensity) was used to evaluate the staining intensity. Associations between LEDGF/p75 expression in tumors and normal tissues were analyzed using Kruskall Wallis's rank sum test. We used TMAs (Imgenex and NDRI) containing specimens corresponding to over 20 major tumor types and normal adjacent tissues. Our data revealed high expression of this protein in tumors of prostate, pancreas, lungs, liver, thyroid, colon, breast and kidney, as compared to corresponding normal adjacent tissues. To further validate our findings, we analyzed LEDGF/p75 expression in the above-mentioned cancers using TMAs (US BIOMAX), each containing multiple tissues specimens of a specific major tumor type, as well as non-cancerous inflammatory disease and normal post-mortem control tissues. Immunohistochemical analysis revealed high expression of LEDGF/p75 in most of the tumor sections as compared to normal control tissues. The normal tissues showed minimal or no staining. The anti-LEDGF/p75 staining was mostly confined to the nucleus, although cytoplasmic staining was also evident in many cells. These results further validate the high expression of LEDGF/p75 in major human cancers and constitute the first step towards defining the biological significance of LEDGF/p75 expression in human cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4667.