Systemic immune‐inflammation indices and MSI‐H/dMMR status in colorectal cancer: Published evidence synthesis with exploratory local clinical and pathological corroboration

Abstract Background Microsatellite instability‐high/deficient mismatch repair (MSI‐H/dMMR) colorectal cancer (CRC) is a biologically distinct subtype with important clinical implications. While tissue‐based assays remain the standard, accessible preoperative surrogate markers are of interest. Systemic inflammatory indices, including the systemic immune‐inflammation index (SII) and neutrophil‐to‐lymphocyte ratio (NLR), have been explored, but their relationship with MSI‐H/dMMR status remains unclear. Objective To evaluate the association between systemic inflammatory indices and MSI‐H/dMMR status using published evidence, local clinical data and pathological corroboration. Methods This study included three components: (1) evidence synthesis of published cohorts comparing inflammatory indices between MSI‐H/dMMR and MSS/pMMR CRC; (2) a retrospective cohort of 28 patients (20 MSS and eight MSI‐H) assessing peripheral blood profiles and exploratory associations; and (3) immunohistochemical quantification of CD8 and myeloperoxidase (MPO) using a Python/OpenCV workflow. Results Six studies ( n = 1598) were included in the NLR synthesis. The pooled random‐effects standardised mean difference was 0.93 (95% confidence interval [CI] 0.016–1.852), suggesting higher NLR in MSI‐H/dMMR cases, although heterogeneity was high ( I 2 = 97.8%). Excluding one influential study reduced the effect to 0.34 (95% CI −0.00 to 0.68). One study of SII suggested a modest increase in MSI‐H/dMMR cases. In the local cohort, lymphocyte count was higher in MSI‐H cases ( p = .009), whereas SII and NLR were lower but not significant. Receiver operating characteristic analysis showed modest discrimination (SII area under the curve [AUC] = 0.675; NLR AUC = 0.656). Pathological quantification showed increased CD8 and reduced MPO/CD8 ratio in MSI‐H tumours. Conclusions MSI‐H/dMMR CRC exhibits a distinct but context‐dependent immune‐inflammatory phenotype. Systemic indices show heterogeneous patterns, while tissue findings indicate a lymphocyte‐enriched microenvironment. These markers may provide supportive immune context, but further validation is required. Trial registration PROSPERO CRD420261323742 ( https://www.crd.york.ac.uk/PROSPERO/view/CRD420261323742 ).