Back to the future: routine morphological assessment of the tumour microenvironment is prognostic in stage II/III colon cancer in a large population-based study

Sean O. Hynes, Helen G. Coleman, Paul J. Kelly, Steven Irwin, Roisin F. O'Neill, Ronan T. Gray, Claire McGready, Philip D. Dunne, Stephen McQuaid, Jacqueline A. James, Manuel Salto-Tellez, Maurice B. Loughrey

Research output: Contribution to journalArticle

17 Citations (Scopus)
209 Downloads (Pure)

Abstract

Aims

Both morphological and molecular approaches have highlighted the biological and prognostic importance of the tumour microenvironment in colorectal cancer (CRC). Despite this, microscopic assessment of tumour microenvironment has not been adopted into routine practice.

Methods and Results

Based on existing evidence, we selected specific morphological features relating to peritumoral inflammatory and stromal responses, agreed criteria for scoring, and assessed these in representative H&E-stained whole tumour sections, from a population-based cohort of 445 stage II/III colon cancer cases. Moderate/severe peritumoral diffuse lymphoid inflammation and Crohn's disease-like reaction were associated with significantly reduced risks of CRC-specific death (adjusted HR 0.48, 95% CI 0.31-0.76, and HR 0.60, 95% CI 0.42-0.84, respectively). The presence of >50% tumour stromal percentage, assessed by global evaluation of tumour area, was associated with a significantly increased risk of CRC-specific death (HR 1.60 95% CI 1.06-2.41). A composite, “fibroinflammatory score” (0-3), combining dichotomised scores of these three features, showed a highly significant association in relation to survival outcomes. Those with a score ≥2 had an almost 2.5 fold increased risk of CRC-specific death (HR 2.44, 95% CI: 1.56-3.81), compared with those scoring zero. These associations were stronger in MSI-high tumours, potentially identifying a subset of MSI-high colon cancers which lack characteristic morphological features and have an associated worse prognosis.

Conclusions

In summary, reporting on H&E staining of selected microscopic features of the tumour microenvironment, independently or in combination, offers valuable prognostic information in stage II/III colon cancer and may allow morphological correlation with developing molecular classifications of prognostic and predictive relevance.

Original languageEnglish
JournalHistopathology
Early online date06 Feb 2017
DOIs
Publication statusEarly online date - 06 Feb 2017

Fingerprint

Tumor Microenvironment
Colonic Neoplasms
Colorectal Neoplasms
Population
Neoplasms
Crohn Disease
Staining and Labeling
Inflammation
N-methylsuccinimide

Cite this

@article{badefc45ea054fb89932d2f8806de8e5,
title = "Back to the future: routine morphological assessment of the tumour microenvironment is prognostic in stage II/III colon cancer in a large population-based study",
abstract = "AimsBoth morphological and molecular approaches have highlighted the biological and prognostic importance of the tumour microenvironment in colorectal cancer (CRC). Despite this, microscopic assessment of tumour microenvironment has not been adopted into routine practice.Methods and ResultsBased on existing evidence, we selected specific morphological features relating to peritumoral inflammatory and stromal responses, agreed criteria for scoring, and assessed these in representative H&E-stained whole tumour sections, from a population-based cohort of 445 stage II/III colon cancer cases. Moderate/severe peritumoral diffuse lymphoid inflammation and Crohn's disease-like reaction were associated with significantly reduced risks of CRC-specific death (adjusted HR 0.48, 95{\%} CI 0.31-0.76, and HR 0.60, 95{\%} CI 0.42-0.84, respectively). The presence of >50{\%} tumour stromal percentage, assessed by global evaluation of tumour area, was associated with a significantly increased risk of CRC-specific death (HR 1.60 95{\%} CI 1.06-2.41). A composite, “fibroinflammatory score” (0-3), combining dichotomised scores of these three features, showed a highly significant association in relation to survival outcomes. Those with a score ≥2 had an almost 2.5 fold increased risk of CRC-specific death (HR 2.44, 95{\%} CI: 1.56-3.81), compared with those scoring zero. These associations were stronger in MSI-high tumours, potentially identifying a subset of MSI-high colon cancers which lack characteristic morphological features and have an associated worse prognosis.ConclusionsIn summary, reporting on H&E staining of selected microscopic features of the tumour microenvironment, independently or in combination, offers valuable prognostic information in stage II/III colon cancer and may allow morphological correlation with developing molecular classifications of prognostic and predictive relevance.",
author = "Hynes, {Sean O.} and Coleman, {Helen G.} and Kelly, {Paul J.} and Steven Irwin and O'Neill, {Roisin F.} and Gray, {Ronan T.} and Claire McGready and Dunne, {Philip D.} and Stephen McQuaid and James, {Jacqueline A.} and Manuel Salto-Tellez and Loughrey, {Maurice B.}",
year = "2017",
month = "2",
day = "6",
doi = "10.1111/his.13181",
language = "English",
journal = "Histopathology",
issn = "0309-0167",
publisher = "Wiley-Blackwell",

}

Back to the future: routine morphological assessment of the tumour microenvironment is prognostic in stage II/III colon cancer in a large population-based study. / Hynes, Sean O.; Coleman, Helen G.; Kelly, Paul J.; Irwin, Steven; O'Neill, Roisin F.; Gray, Ronan T.; McGready, Claire; Dunne, Philip D.; McQuaid, Stephen; James, Jacqueline A.; Salto-Tellez, Manuel; Loughrey, Maurice B.

In: Histopathology, 06.02.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Back to the future: routine morphological assessment of the tumour microenvironment is prognostic in stage II/III colon cancer in a large population-based study

AU - Hynes, Sean O.

AU - Coleman, Helen G.

AU - Kelly, Paul J.

AU - Irwin, Steven

AU - O'Neill, Roisin F.

AU - Gray, Ronan T.

AU - McGready, Claire

AU - Dunne, Philip D.

AU - McQuaid, Stephen

AU - James, Jacqueline A.

AU - Salto-Tellez, Manuel

AU - Loughrey, Maurice B.

PY - 2017/2/6

Y1 - 2017/2/6

N2 - AimsBoth morphological and molecular approaches have highlighted the biological and prognostic importance of the tumour microenvironment in colorectal cancer (CRC). Despite this, microscopic assessment of tumour microenvironment has not been adopted into routine practice.Methods and ResultsBased on existing evidence, we selected specific morphological features relating to peritumoral inflammatory and stromal responses, agreed criteria for scoring, and assessed these in representative H&E-stained whole tumour sections, from a population-based cohort of 445 stage II/III colon cancer cases. Moderate/severe peritumoral diffuse lymphoid inflammation and Crohn's disease-like reaction were associated with significantly reduced risks of CRC-specific death (adjusted HR 0.48, 95% CI 0.31-0.76, and HR 0.60, 95% CI 0.42-0.84, respectively). The presence of >50% tumour stromal percentage, assessed by global evaluation of tumour area, was associated with a significantly increased risk of CRC-specific death (HR 1.60 95% CI 1.06-2.41). A composite, “fibroinflammatory score” (0-3), combining dichotomised scores of these three features, showed a highly significant association in relation to survival outcomes. Those with a score ≥2 had an almost 2.5 fold increased risk of CRC-specific death (HR 2.44, 95% CI: 1.56-3.81), compared with those scoring zero. These associations were stronger in MSI-high tumours, potentially identifying a subset of MSI-high colon cancers which lack characteristic morphological features and have an associated worse prognosis.ConclusionsIn summary, reporting on H&E staining of selected microscopic features of the tumour microenvironment, independently or in combination, offers valuable prognostic information in stage II/III colon cancer and may allow morphological correlation with developing molecular classifications of prognostic and predictive relevance.

AB - AimsBoth morphological and molecular approaches have highlighted the biological and prognostic importance of the tumour microenvironment in colorectal cancer (CRC). Despite this, microscopic assessment of tumour microenvironment has not been adopted into routine practice.Methods and ResultsBased on existing evidence, we selected specific morphological features relating to peritumoral inflammatory and stromal responses, agreed criteria for scoring, and assessed these in representative H&E-stained whole tumour sections, from a population-based cohort of 445 stage II/III colon cancer cases. Moderate/severe peritumoral diffuse lymphoid inflammation and Crohn's disease-like reaction were associated with significantly reduced risks of CRC-specific death (adjusted HR 0.48, 95% CI 0.31-0.76, and HR 0.60, 95% CI 0.42-0.84, respectively). The presence of >50% tumour stromal percentage, assessed by global evaluation of tumour area, was associated with a significantly increased risk of CRC-specific death (HR 1.60 95% CI 1.06-2.41). A composite, “fibroinflammatory score” (0-3), combining dichotomised scores of these three features, showed a highly significant association in relation to survival outcomes. Those with a score ≥2 had an almost 2.5 fold increased risk of CRC-specific death (HR 2.44, 95% CI: 1.56-3.81), compared with those scoring zero. These associations were stronger in MSI-high tumours, potentially identifying a subset of MSI-high colon cancers which lack characteristic morphological features and have an associated worse prognosis.ConclusionsIn summary, reporting on H&E staining of selected microscopic features of the tumour microenvironment, independently or in combination, offers valuable prognostic information in stage II/III colon cancer and may allow morphological correlation with developing molecular classifications of prognostic and predictive relevance.

U2 - 10.1111/his.13181

DO - 10.1111/his.13181

M3 - Article

JO - Histopathology

JF - Histopathology

SN - 0309-0167

ER -