title: Comparison of the prognostic value of measures of the tumor inflammatory cell infiltrate and tumor-associated stroma in patients with primary operable colorectal cancer.
abstract: 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-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). 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%, bothp< 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.
authors.affiliation: Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom; Unit of Experimental Therapeutics, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, United Kingdom.
authors.forename: J H
authors.initials: JH
authors.lastname: Park
authors.affiliation: Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary , Glasgow, United Kingdom.
authors.forename: D C
authors.initials: DC
authors.lastname: McMillan
authors.affiliation: Unit of Experimental Therapeutics, Institute of Cancer Sciences, University of Glasgow, Garscube Estate , Glasgow, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Edwards
authors.affiliation: Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary , Glasgow, United Kingdom.
authors.forename: P G
authors.initials: PG
authors.lastname: Horgan
authors.affiliation: Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary , Glasgow, United Kingdom.
authors.forename: C S D
authors.initials: CS
authors.lastname: Roxburgh
keywords: Colorectal cancer; tumor inflammatory cell infiltrate; tumor microenvironment; tumor stroma