Evaluation of a tumor microenvironment-based prognostic score in primary operable colorectal cancer

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.