The relationship between tumour budding, tumour microenvironment and survival in patients with primary operable colorectal cancer

Van Wyk, H. , Roseweir, A. , Alexander, P. , Park, J. H. , Horgan, P. , McMillan, D. and Edwards, J. (2019) The relationship between tumour budding, tumour microenvironment and survival in patients with primary operable colorectal cancer. Annals of Surgical Oncology, 26, pp. 4397-4404. (doi: 10.1245/s10434-019-07931-6) (PMID:31605345) (PMCID:PMC6863941)

Abstract

Background: Tumor budding is an independent prognostic factor in colorectal cancer (CRC) and has recently been well-defined by the International Tumour Budding Consensus Conference (ITBCC). Objective: The aim of the present study was to use the ITBCC budding evaluation method to examine the relationship between tumor budding, tumor factors, tumor microenvironment, and survival in patients with primary operable CRC. Methods: Hematoxylin and eosin-stained slides of 952 CRC patients diagnosed between 1997 and 2007 were evaluated for tumor budding according to the ITBCC criteria. The tumor microenvironment was evaluated using tumor stroma percentage (TSP) and Klintrup–Makinen (KM) grade to assess the tumor inflammatory cell infiltrate. Results: High budding (n = 268, 28%) was significantly associated with TNM stage (p < 0.001), competent mismatch repair (MMR; p < 0.05), venous invasion (p < 0.001), weak KM grade (p < 0.001), high TSP (p < 0.001), and reduced cancer-specific survival (CSS) (hazard ratio 8.68, 95% confidence interval 6.30–11.97; p < 0.001). Tumor budding effectively stratifies CSS stage T1 through to T4 (all p < 0.05) independent of associated factors. Conclusions: Tumor budding effectively stratifies patients’ survival in primary operable CRC independent of other phenotypic features. In particular, the combination of T stage and budding should form the basis of a new staging system for primary operable CRC. Tumor budding has been defined as a single tumor cell or small cluster of four or fewer tumor cells at the invasive front12,18 and should be considered a promising and strong prognostic factor in colorectal cancer (CRC).19 Widespread reporting of tumor budding has not progressed to routine clinical practice due to a lack of consensus on scoring methods. However, routine reporting is now advocated by using the approach outlined by the International Tumour Budding Consensus Conference (ITBCC), with recommendations for the assessment and reporting of tumor budding in CRC.6 The ITBCC recommends that tumor budding should be included in future CRC guidelines and protocols and should be considered, along with other clinicopathological factors, in a multidisciplinary setting. The recent dataset for histopathological reporting of CRC by the royal pathologist stated that they would reconsider reporting tumor budding when new data become available.4 The tumor microenvironment also plays an important role in CRC outcomes. Marked peritumoral inflammation has been associated with favorable outcome,3,14 while the presence of a high tumor stroma percentage (TSP) has been validated as a stage-independent marker of reduced survival in patients with primary operable CRC.7,8. Both contribute to the development of a tumor microenvironment score that can potentially supplement the current TNM staging system.9 The aim of this study was to assess the proposed method by ITBCC in clinical practice and investigate the relationship between tumor budding and tumor factors, tumor microenvironment, and survival in primary operable CRC.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Park, Mr James and Horgan, Professor Paul and Alexander, Mr Peter and McMillan, Professor Donald and Van Wyk, Dr Hester and Roseweir, Dr Antonia and Edwards, Professor Joanne
• Authors: Van Wyk, H., Roseweir, A., Alexander, P., Park, J. H., Horgan, P., McMillan, D., and Edwards, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Annals of Surgical Oncology
• Publisher: Springer International Publishing
• ISSN: 1068-9265
• ISSN (Online): 1534-4681
• Published Online: 11 October 2019
• Copyright Holders: Copyright © The Authors 2019
• First Published: First published in Annals of Surgical Oncology 26:4397-4404
• Publisher Policy: Reproduced under a Creative Commons license