Comprehensive phenotyping of intratumoral fibrosis in gastric carcinomas with poorly differentiated histology: associations with clinicopathological features

Background Fibrosis is a prominent component of the gastric cancer microenvironment; however, its intratumoral patterns remain poorly characterized. In this study, we employed multidimensional phenotypic profiling to provide a comprehensive characterization of tumour‐associated fibrosis and evaluate its association with histological subtypes and clinical outcomes in gastric carcinomas with poorly differentiated histology. Methods Of the 392 patients with gastric cancer who underwent gastrectomy at our centre during the study period, 30 patients with T3 tumours were selected for analysis, comprising signet‐ring cell carcinoma (SRC), poorly differentiated adenocarcinoma, non‐solid type (por2), as well as poorly differentiated adenocarcinoma, solid type (por1). Fibrosis phenotypes were quantified using FibroNest™, a digital pathology platform enabling single‐fibre assessment of collagen quantity, morphology and structural organization. Key quantitative fibrosis traits (qFTs) were integrated into a phenotypic fibrosis composite score for gastric cancer (Ph‐FC‐GC). Results Ph‐FCS‐GC differentiated the overall fibrosis patterns of por1 from those of SRC and por2, although no clear differences in individual fibrosis features were observed between por2 and SRC. Importantly, Ph‐FCS‐GC also effectively discriminated between tumours with and without lymph node metastasis. qFT analysis revealed previously uncharacterized heterogeneity in collagen morphometrics, such as fibre length and branching, in non‐metastatic tumours, whereas metastatic tumours showed more uniform architectures. Tumours with 3‐year recurrence exhibited lower porous area ratios and more spatially ordered collagen networks, indicating denser, more organized fibrosis than non‐recurrent tumours. Conclusions Collagen morphology and architecture differ according to histological subtype and may provide prognostic insights into lymph node metastasis and recurrence in gastric cancer.