Evaluation of a Tumor Microenvironment–Based Prognostic Score in Primary Operable Colorectal Cancer

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Abstract
Purpose: The tumor microenvironment is recognized as an important determinant of progression and outcome in colorectal cancer. The aim of the present study was to evaluate a novel tumor microenvironment–based prognostic score, based on histopathologic assessment of the tumor inflammatory cell infiltrate and tumor stroma, in patients with primary operable colorectal cancer. Experimental Design: Using routine pathologic sections, the tumor inflammatory cell infiltrate and stroma were assessed using Klintrup–Mäkinen (KM) grade and tumor stroma percentage (TSP), respectively, in 307 patients who had undergone elective resection for stage I–III colorectal cancer. The clinical utility of a cumulative score based on these characteristics was examined. Results: On univariate analysis, both weak KM grade and high TSP were associated with reduced survival (HR, 2.42; P = 0.001 and HR, 2.05; P = 0.001, respectively). A cumulative score based on these characteristics, the Glasgow Microenvironment Score (GMS), was associated with survival (HR, 1.93; 95% confidence interval, 1.36–2.73; P < 0.001), independent of TNM stage and venous invasion (both P < 0.05). GMS stratified patients in to three prognostic groups: strong KM (GMS = 0), weak KM/low TSP (GMS = 1), and weak KM/high TSP (GMS = 2), with 5-year survival of 89%, 75%, and 51%, respectively (P < 0.001). Furthermore, GMS in combination with node involvement, venous invasion, and mismatch repair status further stratified 5-year survival (92% to 37%, 93% to 27%, and 100% to 37%, respectively). Conclusions: The present study further confirms the clinical utility of assessment of the tumor microenvironment in colorectal cancer and introduces a simple, routinely available prognostic score for the risk stratification of patients with primary operable colorectal cancer. Clin Cancer Res; 21(4); 882–8. ©2014 AACR.

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