Abstract 562: Stromal TLR4 and IL 6 expression as potential prognostic inflammation-associated markers for colo-rectal cancer progression

Abstract

Abstract Epidemiological studies suggest that chronic inflammatory conditions constitute pre-neoplastic conditions. To study how chronic inflammation could affect tumor growth and progression, we quantified the presence of inflammatory cells and expression of inflammatory cytokines by immunohistochemistry on archival tissue samples from 116 patients. We considered 13 cases of ulcerative colitis, 34 tubular or tubulo-villous adenomas with low or high grade dysplasia, and 53 infiltrating adenocarcinomas with T1, T2, T3, and T4 staging. Sixteen specimens of healthy mucosa resected along with the cancerous tissue were used as controls. We investigated expression of CD68 (macrophages), CD15 (neutrophils), CD31 (endothelial cells), Interleukin 6 (IL-6), Hepatocyte Growth Factor (HGF), and Toll-Like Receptor 4 (TLR-4). We considered 3 specific tissue compartments: epithelial, stromal and endothelial (vessel associated). Statistical differences between individual cell groups were determined using an unpaired two way t-test (Mann-Whitney). Progression from healthy tissue to ulcerative colitis was characterized by a massive inflammatory-angiogenic reaction, as for a significant increase in expression of inflammation markers, paralleled by down-regulation of a potential suppressive molecule, HGF. Subsequently, a progressive increase in cells expressing CD68, CD15, TLR-4, and IL6 were found in the passage from adenoma to adenocarcinoma. Adenocarcinoma patients that expressed high levels of TLR-4 in the stromal compartment had a significantly increased risk of relapse within 40 months. Moreover, in the subgroup of adenocarcinoma patients with a diagnosis of pT3 colon cancer (the most frequent pT), those with higher levels of TLR-4 in the tumor stroma showed increased risk for a relapse within 15 months. These data suggest that inflammation correlates with progression in colorectal cancer, and that TLR-4 represents a potential prognostic marker of colo-rectal cancer progression. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 562.