ArticleAmerican journal of cancer research2026
Correlation of tumor-infiltrating lymphocyte spatial distribution patterns with HER2 expression status and prognostic significance in gastric adenocarcinoma: a retrospective study based on digital pathology.
Article in American journal of cancer research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe spatial distribution of tumor-infiltrating lymphocytes (TILs) has prognostic value in solid tumors, but its relationship with HER2 status in gastric adenocarcinoma remains poorly characterized.
methodsTIL densities in the tumor center (CT) and at the invasive margin (IM) were assessed on H&E-stained slides using QuPath, and the edge/center ratio (E/C ratio = IM-TILs/CT-TILs) was calculated. The optimal cut-off for E/C ratio was determined by maximizing the log-rank statistic. Survival analyses were performed using Kaplan-Meier and Cox regression.
resultsThe HER2-positive group (n = 35) exhibited significantly lower CT-TILs (11.92% vs. 20.98%, P < 0.001) and a higher E/C ratio (2.11 vs. 1.25, P < 0.001) than the HER2-negative group (n = 165). Using an optimal cut-off of 1.57, high E/C ratio was associated with significantly worse overall survival (OS) in the whole cohort (median 14.64 vs. 42.87 months; log-rank P < 0.001). Multivariate Cox regression, adjusting for clinicopathological factors, revealed that the E/C ratio as a continuous variable was independently prognostic (HR = 1.398, P < 0.001), and a significant interaction between HER2 status and E/C ratio was observed (HR = 1.844, P = 0.001). Dichotomization at E/C > 1.57 provides significant prognostic stratification, an effect that is modified by HER2 status; however, due to the small HER2-positive subgroup, these findings require validation in larger independent cohorts.
conclusionsHER2-positive gastric adenocarcinoma exhibits an "edge-limiting" immune phenotype with elevated E/C ratio. Digital assessment of TILs on routine H&E sections is simple and promising for clinical translation.
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