However, the ROC curve also highlights a relatively poor discrimination of survivors and non-survivors at 5-year follow up with an AUC value of 0.59 (95%CI: 0.52�C0.67). A high-budding index was significantly associated Cabozantinib Sigma with a more advanced pT stage (P=0.017), with the presence of lymph node metastasis (P=0.002), with the presence of vascular invasion (P=0.028) and with an infiltrating tumour border configuration (P=0.005) (Table 3). Patients with MSI-H cancers were significantly less prone to a high tumour-budding index (P=0.022), whereas no association was observed with KRAS or BRAF mutation. The odds of death from disease at 5 years in the group with a high-budding index was OR (95%CI)=1.89 (1.1�C3.3) compared with those with a low index (P=0.022) (Table 4).

In all, 5-year disease-specific survival rate of patients with high and low tumour-budding index was 53.0 (95%CI 42�C63) and 63.9 (95%CI 57�C70), suggesting a significantly worse prognosis in patients with high tumour-budding index (P=0.033) (Figure 2B). In patients with MSS/MSI-L tumours, a high-budding index was related to more advanced pT stage (P=0.019), pN stage (P=0.002), vascular invasion (P=0.004) and an infiltrating tumour border configuration (P=0.021) and worse survival in univariate analysis (P=0.02). In MSI-H patients, the high tumour-budding index was only related to an infiltrating tumour border configuration (P=0.015). Figure 2 Cohort 1. (A, C and E): Receiver operating characteristic (ROC) curves highlighting the ability of tumour budding (A), CD8+ lymphocytes (C) and CD8+/buds index (E) to discriminate survivors and non-survivors.

AUC=area under the … Table 3 Association of budding index, CD8+ index and CD8+/buds index with clinico-pathological features �C Cohort 1 (n=279) Table 4 Comparison of the discriminatory ability of each feature for identifying survivors and non-survivors at 5-year follow up CD8+ index A high CD8+ index was characterised by the presence of at least 40 CD8+ cells per �� 40 field (Figure 2C). The discriminatory ability of CD8+ as indicated by the AUC was 0.64 (95%CI 0.59�C0.7), suggesting an improvement compared with the budding index alone. The odds of death from disease at 5 years was OR (95%CI)=3.18 (1.8�C5.5) in patients with a low compared with a high CD8+ index. A high CD8+ index was associated with significantly more frequent peritumoural lymphocytic inflammation at the tumour front (P=0.

002), with MSI-H status (P=0.033) and marginally with BRAF mutation. Patients with a high CD8+ index demonstrated a significantly prolonged survival time compared with those with a low CD8+ index (P<0.001) (Figure 2D). In MSS/MSI-L and MSI-H patients, the CD8+ index was not linked to any Batimastat features of tumour progression although in MSS/MSI-L those with a high CD8+ index experienced a significant prolonged survival time (P=0.011).