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-M€ akinen (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 ¼ 0.001 and HR, 2.05; P ¼ 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 ¼ 0), weak KM/ low TSP (GMS ¼ 1), and weak KM/high TSP (GMS ¼ 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.

Diagnostic value of inflammatory cell infiltrates, tumor stroma percentage and disease-free survival in patients with colorectal cancer

“…We also assessed the overall parameters of inflammatory cell infiltrate and TSP by GMS, which did not confirmed statistically significant differences in DFS. Our observations are contrary to the results of Park et al (4). These differences may be due to sample size, nationality of the selected population and the scope of the TNM staging of patients enrolled in the study.…”

“…The prognosis of patients is performed by staging of primary tumor and the involvement of metastases in the lymph nodes and distant organs by standard classification of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) classification based upon the tumor-node-metastasis (TNM) (2). However, recent reports in the literature indicated that a considerable heterogeneity of the primary tumor of colon cancer requires a more detailed qualitative analysis, all of its components such as inflammatory response and connective tissue stroma (3,4).…”

Comparison of the prognostic value of measures of the tumor inflammatory cell infiltrate and tumor-associated stroma in patients with primary operable colorectal cancer

“…Histopathological reporting confirmed stage I, stage II and stage III disease in 7%, 52% and 41% of patients respectively. Mismatch repair status has previously been reported in a subset of this cohort and was available for 205 patients; 17 30 patients (15%) had mismatch repair deficient colorectal cancer.…”

“…13 Indeed, combined assessment of KM grade and TSP, termed the Glasgow Microenvironment Score (GMS), stratified survival greater than either measure alone, and in particular further stratified survival of those patients with a weak local inflammatory cell infiltrate. 17 However, whether inclusion of a potentially more detailed measure of the inflammatory cell infiltrate, such as the Immunoscore, may alter the prognostic value of the tumor-associated stroma is not clear. Therefore, the present study of patients undergoing potentially curative resection of stage I-III colorectal cancer has two aims: to compare the prognostic value of assessment of the inflammatory cell infiltrate using the KM grade and the Immunoscore, and to examine the clinical utility of combined assessment of the inflammatory cell infiltrate and TSP.…”

Obesity-associated cancer: an immunological perspective

“…It may be useful to evaluate the level of immune involvement in the tumour microenvironment, and evaluate the degree of immune cell dysregulation prior to devising a patient treatment plan. Indeed, evaluation of immunological parameters is presently in development as a prognostic aid, and shows superior predictive ability compared with traditional histopathological staging methods in colorectal cancer (164)(165)(166) . Galon et al show that evaluation of the type, density and location of immune cell infiltration into tumours can allow prediction of patient survival (165) .…”