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 generalised inflammatory cell
infiltrate (the Klintrup-Mäkinen (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). 246 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-based assessment in patients undergoing
resection of stage I-III CRC. Furthermore, assessment of the tumor-associated stroma, using
TSP, further improves prediction of outcome
