Clinical and immunopathological evaluation and its comparison with consensus molecular subtypes of colorectal cancer.

3594 Background: This study aims to elucidate the prognostic impact of the immunoscore within the context of consensus molecular subtypes (CMS), tumor budding (TB), and macrophage infiltration in colorectal cancer (CRC), addressing a gap in current research. Methods: A retrospective observational study analyzing 255 colorectal cancer cases. Demographic, histopathological, and clinical variables were examined. Molecular classification, immunoscore, and macrophage infiltration were determined via immunohistochemistry. The study adhered to ethical guidelines and received approval from our ethics committee. CMS assessment used automated staining for specific markers, with molecular subtype determined using an online classifier (Ten Hoorn et al.). Immunoscore calculation involved evaluating CD3+ and CD8+ immune cells, classifying patients into low or intermediate-high groups (Jiang et al.). Macrophage assessment focused on CD163+ cells, categorizing them as spindle-cell and round-cell. Statistical analysis employed SPSS, using descriptive statistics, chi-square tests, Kaplan-Meier survival curves, and multivariate analyses. Results: In this study of 255 colorectal cancer patients, predominantly with localized disease, 34.9% had stage III disease. Conventional and serrated adenocarcinomas were the main histological subtypes. CMS classification revealed mostly CMS2-3 (69.4%), with relapse occurring across all subtypes. Low immunoscore was common in conventional and serrated histology and CMS2/3, while MSI-H correlated with intermediate-high immunoscore. Tumor budding (TB) was prevalent in relapsed patients, especially in CMS2/3 and CMS4, and associated with serrated histology. Metastatic patterns varied by CMS subtype, with TB > 20 foci linked to hepatic metastases. CD163 macrophage infiltration was associated with CMS1 and CMS2/3, and a high immune score. Over 9.6 years of follow-up, tumor budding was associated with overall and relapse-free survival, while CMS was linked to overall survival. Immunoscore showed no association with survival outcomes. Conclusions: This cohort shows heterogeneous disease progression and prognosis, with CMS2/3 exhibiting high tumor budding and relapse rates, especially in serrated histology. Molecular subtypes have distinct metastatic patterns: CMS1 to the peritoneum, CMS2/3 to the liver, and CMS4 to both. Relapsed CMS2/3 cases had low immunoscore, while CD163+ macrophage infiltration correlated with higher immune scores in CMS1 and CMS2/3, highlighting the complex interactions between molecular subtypes, immune responses, and tumor behavior.