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

Background: Tumour budding has been reported to reflect invasiveness, metastasis and unfavourable prognosis in colorectal cancer. The aim of the study was to examine the relationship between tumour budding and clinicopathological characteristics, tumour microenvironment and survival in patients with primary operable colorectal cancer. Methods: A total of 303 patients from a prospective data set of patients with primary operable colorectal cancer were included in the study. The presence of budding was determined through assessment of all tumour-containing H&E slides and the number of tumour buds was counted using a 10 high-powered field method. Routine pathologic sections were used to assess: tumour necrosis, the tumour inflammatory cell infiltrate using Klintrup-Makinen (KM) grade and tumour stroma percentage (TSP) combined as the Glasgow Microenvironment Score (GMS). Results: High-grade tumour budding was present in 39% of all tumours and in 28% of node-negative tumours respectively. High-grade budding was significantly associated with T stage (P<0.001), N stage (P<0.001), TNM stage (P<0.001), serosal involvement (P<0.001), venous invasion (P<0.005), KM grade (P = 0.022), high tumour stroma (P<0.001) and GMS (P<0.001). Tumour budding was associated with reduced cancer-specific survival (CSS) (HR = 4.03; 95% confidence interval (CI), 2.50-6.52; P<0.001), independent of age (HR = 1.47; 95% CI, 1.13-1.90; P = 0.004), TNM stage (HR = 1.52; 95% CI, 1.02-2.25; P = 0.040), venous invasion (HR = 1.73; 95% CI, 1.13-2.64; P = 0.012) and GMS (HR = 1.54; 95% CI, 1.15-2.07; P = 0.004). Conclusions: The presence of tumour budding was associated with elements of the tumour microenvironment and was an independent adverse prognostic factor in patients with primary operable colorectal cancer. Specifically high tumour budding stratifies effectively the prognostic value of tumour stage, venous invasion and GMS. Taken together, tumour budding should be assessed routinely in patients with primary operable colorectal cancer.