The prognostic value of tumour stroma ratio and tumour budding in stage II colon cancer. A nationwide population-based study

Ann Christina Eriksen,René Depont Christensen,Henrik Hager,Torben F Hansen,Sanne Kjær-Frifeldt,Jan Lindebjerg,Flemming B Sørensen

doi:10.1007/s00384-018-3076-9

Abstract

PurposeHigh-risk patients with stage II colon cancer (CC) may benefit from adjuvant chemotherapy, but additional prognostic markers are needed for better stratification. We investigated the prognostic value of tumour stroma ratio (TSR) and tumour budding (TB).MethodsA nationwide population-based cohort of 573 patients with stage II CC was included. TSR was scored on hematoxylin and eosin sections as low TSR (> 50% stroma) and high TSR (≤ 50% stroma). TB was evaluated in hotspots on pan-cytokeratin stained sections in 10 high power fields (HPF) at the invasive front and classified by the mean number of buds per HPF as high grade budding (≥ 10 buds) or low-grade budding (< 10 buds). The prognostic value was investigated in Cox proportional hazard models for recurrence-free survival (RFS) and overall survival (OS).ResultsLow TSR was associated with worse RFS (HR = 1.342 (95% CI 1.006–1.791), p = 0.045) and OS (HR = 1.376 (95% CI 1.016–1.862), p = 0.039). Furthermore, an association was found between low TSR and microsatellite stabile tumours (p < 0.001). The mean number of buds per HPF was associated to TSR with increasing number of buds related to a lower TSR (p = 0.026). No statistically significant prognostic impact of TB regarding OS or RFS was detected.ConclusionsTSR provided valuable prognostic information, and adding TSR to the current risk stratification may contribute to better patient selection. The estimates of TSR and TB were found to be associated, but no prognostic value of TB was documented.

Highlights

Odense, DenmarkColon cancer (CC) is one of the most prevalent cancers in the Western world, and approximately one third of the patients are diagnosed with stage II disease
Low Tumour stroma ratio (TSR) was associated with reduced recurrence-free survival (RFS), hazard ratio (HR) = 1.342, independent of age, T-stage, localization, perforation and Microsatellite instability (MSI) status
Population-based cohort exclusively consisting of patients resected for stage II CC, and to avoid possible confounding we excluded patients treated with adjuvant chemotherapy and patients with other known malignancies

Summary

Introduction

DenmarkColon cancer (CC) is one of the most prevalent cancers in the Western world, and approximately one third of the patients are diagnosed with stage II disease. Current international guidelines (ASCO and ESMO) recommend adjuvant treatment limited to patients at high risk of recurrence identified by at least one of the following clinical characteristics: pT4 tumours; extramural vascular, lymphatic or perineural invasion; poorly differentiated histology; and obstruction or tumour perforation and lymph node sampling lower than 12 [1, 2]. These risk factors have been found insufficient for ideal selection of patients for adjuvant therapy [3], Int J Colorectal Dis (2018) 33:1115–1124 and there is a need for additional prognostic markers for better clinical management of patients with stage II CC. The prognostic impact of TSR in a large unbiased population-based cohort of stage II CC is currently unknown

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