Tumour deposits in colorectal carcinoma are associated with immune evasion and dose-dependent adverse prognosis beyond nodal status

Tumour deposits (TDs) are established adverse prognostic features in colorectal carcinoma, yet their biologic significance and integration into current nodal staging systems remain controversial. Although TD burden has been associated with adverse prognosis beyond lymph node metastasis, its incremental staging relevance and the immune microenvironmental features of the primary tumour that may underlie the aggressive behaviour of TD-positive tumours remain incompletely defined.

We evaluated 845 consecutive colorectal carcinomas resected at a single institution between 2007 and 2015. Clinicopathologic features, TD burden and disease-specific survival (DSS) were analysed. Immune profiling was performed on tissue microarrays using immunohistochemistry for CD8, CD163, FoxP3, LAG3, PD-L1, HLA class I, HLA class II, and beta-2-microglobulin (B2M), with automated quantitative image analysis.

Among 825 patients with available data, TDs were identified in 106 cases (12.8%) and were significantly associated with adverse clinicopathologic features, including advanced T stage, lymph node metastasis, extramural venous invasion, perineural invasion, and distant metastasis. TD-positive tumours demonstrated significantly worse 5-year DSS compared with TD-negative tumours (45.8 vs. 81.0%, p < 0.001). Increasing TD burden conferred a dose-dependent adverse impact on DSS (p < 0.001), including within lymph node-positive disease. Within stage III tumours, TD burden stratified outcome beyond conventional nodal categories with pN1 tumours lacking TDs approximating stage II survival and pN2 tumours with TDs approaching stage IV outcomes. In this context, TD-positive tumours showed reduced intratumoral CD8+ T-cell infiltration, decreased tumour cell B2M expression and increased tumour cell PD-L1 expression, consistent with an immune-evasive phenotype.

TDs are associated with adverse clinicopathologic features, immune-evasive tumour microenvironments and poor disease-specific survival in colorectal carcinoma. Quantitative TD burden provides additional prognostic information beyond nodal status, supporting the incorporation of TD burden into future staging paradigms.