Tumour budding/T cell infiltrates in colorectal cancer: proposal of a novel combined score

Aims The tumour-node-metastasis classification system is used for prognostication purposes and to guide patient management. However, in colorectal cancer (CRC), additional markers are needed to stratify prognostic subgroups. Two promising markers have emerged from large bodies of research: tumour budding and T cell host response (CD3, CD8 and CD45RO infiltrates). However, attempts to combine these two parameters have been sparse. The aim of this study was to perform an assessment of potential protagonists that could be used in a combined score (budding/T cell score, BTS). Methods and results This descriptive, retrospective study was performed on a multipunch tissue microarray containing material from 345 patients with stages I-IV CRC. Areas from tumour centre, front and microenvironment were stained for pancytokeratin/CD3, pancytokeratin/CD8 and pancytokeratin/CD45RO. Tumour buds were scored manually and T cell infiltrates digitally using open-source software. Tumour buds, T cell counts and combined BTS were associated with clinicopathological features and overall survival (OS). A higher combined BTS score (buds/CD8, tumour centre) performed better than budding or CD8/CD3 alone in predicting nodal metastases (P < 0.0001, OR = 1.466, 95% CI = 1.115-1.928). Only higher BTS (buds/CD3) were significantly associated with poorer OS on multivariate analysis (P = 0.012, hazard ratio = 1.218, 95% confidence interval = 1.044-1.419). Conclusions Although CD8(+)/CD3(+) T cells are predictive of tumour biology in CRC, we found a combined BTS to be stronger in predicting survival and certain features with high clinical relevance, such as nodal metastases, in comparison to budding or T cells alone. Further studies combining T cell infiltrates and tumour budding are necessary to optimise risk assessment of CRC.