Abstract 4987: Immunoscore of CD8/CD45RO in pre-operative biopsy specimens predicts TNM-stage in primary colorectal cancer.

Abstract

Abstract Background: Colonoscopy and biopsy are the standard procedure for primary diagnosis of colorectal cancer (CRC), but prognostic biomarkers based on biopsy material are still missing. The tumor microenvironment has been shown to play a major role in the pathogenesis of CRC. Therefore, we hypothesized that an immunoscore of CD8+ T-effector and CD45RO+ memory T-cell infiltrates in pre-operative biopsy specimens could have an impact on the pre-operative management of CRC patients by predicting TNM-stage. Methods: Intraepithelial (i) and stromal (s)CD8+ and CD45RO+ T-cells were visualized in biopsy specimens of 134 well characterized CRC patients by immunohistochemistry and quantified in 5 high-power-fields each of the highest density of immune cell infiltration. Cut-off scores for prediction of pN, pM and pT in the matched resection specimen were established using Classification and Regression Tree (CART) analysis. Infiltration of CD8+ and CD45RO+ T-cells in each compartment was assessed for prediction of TNM stage, lymphovascular invasion and tumor grade. Results: High numbers of infiltrating sCD45RO T-cells in biopsy material were associated with earlier T-stage in the matched resection specimen(p<0.0001) as well as with earlier tumor grade (p=0.0223) and absence of distant metastasis (p=0.0177; specificity=62.5% and positive predictive value (PPV)=93%). High total (t) numbers of infiltrating CD8-T cells in biopsy material were strongly predictive of absence of nodal metastasis (p=0.0182) as well as absence of lymphatic invasion (p=0.0201). Combined analysis of tCD8 and tCD45RO with pN led to 100% specificity and PPV. No association of CD8+ and CD45R0+ T-cell-infiltration with vascular invasion was observed. In contrast, absence of both CD8+ and CD45RO+ T-cells in pre-operative biopsies predicted frequent nodal and distant metastatic spread, advanced T-stage and lymphovascular invasion in the matched resection specimen. Conclusion: Total CD8 counts and sCD45RO in pre-operative biopsy specimens allows prediction of essential clinical characteristics of primary CRC in the matched resection specimen including full TNM-stage and lymphatic invasion. Analysis of total CD8+ and sCD45RO+ in pre-operative biopsies may thereby provide a decisive indicator for risk stratification of CRC patients in the preoperative setting. Citation Format: Viktor H. Koelzer, Alessandro Lugli, Heather Dawson, Markus Borner, Daniel Inderbitzin, Inti Zlobec. Immunoscore of CD8/CD45RO in pre-operative biopsy specimens predicts TNM-stage in primary colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4987. doi:10.1158/1538-7445.AM2013-4987