Table 2_CD163-positive macrophage enrichment is associated with mismatch repair deficiency and adverse pathologic features in early-stage endometrioid endometrial carcinoma: a retrospective cohort study.docx

Exploratory DFS analyses included single-marker and combined Cox models, formal MMR-by-TAM interaction testing, and comparison of models with and without continuous CD163-positive TAM density.</p>Results<p>Among 254 patients assessed, 236 were included. MMR protein expression was retained in 172 tumors (72.9%), whereas 64 (27.1%) were classified as dMMR. CD163-positive TAM density was higher in dMMR than pMMR tumors (median, 76 vs 47 cells/HPF; P<0.001), and high TAM infiltration was more frequent in dMMR tumors (44/64, 68.8% vs 71/172, 41.3%; P<0.001).

After adjustment for age, FIGO stage, tumor grade, tumor size, and deep myometrial invasion, dMMR remained associated with high macrophage infiltration (adjusted OR, 2.27; 95% CI, 1.19–4.18; P = 0.008). High macrophage infiltration was associated with grade 3 histology, deep myometrial invasion, LVSI, and the composite adverse pathologic feature; the association with the composite endpoint persisted after adjustment (adjusted OR, 1.78; 95% CI, 1.01–3.14; P = 0.047).

During follow-up, 26 DFS events occurred. In exploratory Cox analyses, dMMR was associated with DFS (adjusted HR, 2.76; 95% CI, 1.25–6.10; P = 0.012), whereas continuous CD163-positive TAM density was not (adjusted HR per 10 cells/HPF, 1.04; 95% CI, 0.97–1.12; P = 0.281), and addition of CD163-positive TAM density did not significantly improve model fit beyond MMR status (likelihood-ratio P = 0.279). The dMMR/high-TAM phenotype retained an exploratory association with DFS in the conventional model (adjusted HR, 2.21; 95% CI, 1.02–4.81; P = 0.044), but the association was attenuated after additional adjustment for adjuvant therapy (HR, 2.04; 95% CI, 0.93–4.52; P = 0.075).</p>Conclusions<p>IHC-defined dMMR was associated with increased CD163-positive macrophage infiltration, and higher TAM infiltration was associated with adverse pathologic features.

DFS findings were exploratory and did not establish incremental prognostic value of CD163-positive TAM infiltration beyond MMR status; larger externally validated cohorts are required to assess prognostic relevance.</p>