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

The aim of the present study was to compare the clinical utility of two measures of the inflammatory cell infiltrate - a H&E-based assessment of the generalized inflammatory cell infiltrate (the Klintrup-Makinen (KM) grade), and an immunohistochemistry-based assessment of combined CD3(+) and CD8(+) T-cell density (the "Immunoscore"), in conjunction with assessment of the tumor stroma percentage (TSP) in patients undergoing resection of stage I-III colorectal cancer (CRC). Two hundred and forty-six patients were identified from a prospectively maintained database of CRC resections in a single surgical unit. Assessment of KM grade and TSP was performed using full H&E sections. CD3(+) and CD8(+) T-cell density was assessed on full sections and the Immunoscore calculated. KM grade and Immunoscore were strongly associated (p < 0.001). KM grade stratified cancer-specific survival (CSS) from 88% to 66% (p = 0.002) and Immunoscore from 93% to 61% (p < 0.001). Immunoscore further stratified survival of patients independent of KM grade from 94% (high KM, Im4) to 60% (low KM, Im0/1). Furthermore, TSP stratified survival of patients with a weak inflammatory cell infiltrate (low KM: from 75% to 47%; Im0/1: from 71% to 38%, both p < 0.001) but not those with a strong inflammatory infiltrate. On multivariate analysis, only Immunoscore (HR 0.44, p < 0.001) and TSP (HR 2.04, p < 0.001) were independently associated with CSS. These results suggest that the prognostic value of an immunohistochemistry-based assessment of the inflammatory cell infiltrate is superior to H&E-base dassessment in patients undergoing resection of stage I-III CRC. Furthermore, assessment of the tumor-associated stroma, using TSP, further improves prediction of outcome.