CD8+lymphocytes/tumour-budding index: an independent prognostic factor representing a 'pro-/anti-tumour' approach to tumour host interaction in colorectal cancer

BACKGROUND: The tumour-host interaction at the invasive front of colorectal cancer, including the epithelial-mesenchymal transition and its hallmark 'tumour budding', is an important area of investigation in terms of prognosis. The aim of this study was to determine the prognostic impact of a 'pro-/anti-tumour' approach defined by an established 'pro-tumour' (tumour budding) and host-related 'anti-tumour' factor of the adaptive immunological microenvironment (CD8+ lymphocytes). METHODS: Double immunostaining for CK22/CD8 on whole tissue sections (n = 279; Cohort 1) and immunohistochemistry for CD8+ using tissue microarrays (n = 191; Cohort 2) was carried out. Tumour buds, CD8+ and CD8+ T-lymphocytes : tumour buds indices were evaluated per high-power field. RESULTS: In Cohort 1, a low-CD8+/buds index was associated with lymph node metastasis (P < 0.001), vascular invasion (P = 0.009), worse survival in univariate (P < 0.001) and multivariable (P < 0.001) analysis, and furthermore in lymph node-negative patients (P = 0.002). In Cohort 2, the CD8+/buds index was associated with T stage (P < 0.001), N stage (P = 0.041), vascular invasion (P = 0.005) and survival in patients with TNM stage II (P = 0.019), stage III (P = 0.004), and adjuvantly untreated (P = 0.009) and treated patients (P < 0.001). CONCLUSION: The CD8+ lymphocyte : tumour-budding index is an independent prognostic factor in colorectal cancer and a promising approach for a future prognostic score for patients with this disease. British Journal of Cancer (2009) 101, 1382-1392. doi:10.1038/sj.bjc.6605318 www.bjcancer.com Published online 15 September 2009 (C) 2009 Cancer Research UK