566P - Prognostic Significance of Tumour-Associated Immune Response Gene Expression, Esr1 and Clinicopathologic Parameters in Stage Ii/Iii Colorectal Cancer: a Translational Research Study of the Hellenic Cooperative Oncology Group (Hecog)

Abstract

ABSTRACT Aim: Tumour-associated immune response and colon cancer site emerge as parameters impacting on disease biology and patient outcome. Methods: mRNA gene expression of immune response (IR) genes (CD3Z, CD8, CXCL9, CXCL13, IGHM, FOXP3), SNAI2 and ESR1 were quantified by RTqPCR in formalin-fixed tumours of 408 oxaliplatin-treated patients with stage II/III colorectal cancer (trial ACTRN12610000509066). Results were submitted to hierarchical clustering and analysed. Results: We selected a mRNA gene signature (mRNA 2-cluster immunoscore, mIS2) based on CD3Z and CD8 expression (Cluster 2: upregulated CD3Z CD8 expression; Cluster 1: more heterogeneous but overall downregulated CD3Z CD8 expression). Partitioning analysis including age, stage, site, mIS2 and KRAS gene mutation, revealed that tumour stage, tumour site and mIS2 identified eight patient populations with distinct DFS (p MULTIVARIATE ANALYSIS HR for relapse P-value HR for death P-value STAGE_SITE_mIS2 0.0008 0.0008 Stage II Right mIS2-downreg 0.23 0.1702 0.17 0.09 Stage II Right mIS2-upreg 0.19 0.1188 0.00 0.98 Stage II Left mIS2-downreg 0.26 0.0466 0.22 0.02 Stage II Left mIS2-upreg 0.62 0.4803 0.46 0.25 Stage III Right mIS2-downreg 3.00 0.0152 2.62 0.02 Stage III Right mIS2-upreg 0.79 0.7355 1.50 0.43 Stage III Left mIS2-downreg 1.43 0.4001 1.04 0.91 Stage III Left mIS2-upreg 1 1 HIGH TUMOUR MRNA EXPRESSION OF ESR1 2.91 0.0003 1.95 0.02 PRESENCE OF NECROSIS 0.42 0.0068 0.39 0.002 Conclusions: The prognostic significance of tumour mRNA-based CD3 and CD8 immune response signature may be distinct in different stages and different sites of colon cancer. Disclosure: R. Wirtz: Stocks at Stratifyer Molecular Pathology, Cologne, Germany. All other authors have declared no conflicts of interest.