Clinicopathologic Characteristics of Trop Family Proteins (Trop-2 and EpCAM) in Gastric Carcinoma.

Abstract

Purpose: Trop family proteins, including epithelial cell adhesion molecule (EpCAM) and Trop-2, have garnered attention as potential therapeutic and diagnostic targets for various malignancies. This study aimed to elucidate the clinicopathological significance of these proteins in gastric carcinoma (GC) and to reinforce their potential as biomarkers for patient stratification in targeted therapies.

Materials and methods: Immunohistochemical (IHC) analyses of EpCAM and Trop-2 were performed on GC and precancerous lesions, following rigorous orthogonal validation of the antibodies to ensure specificity and sensitivity.

Results: Strong membranous staining (3+) for Trop-2 was observed in 49.3% of the GC cases, whereas EpCAM was strongly expressed in almost all cases (93.2%), indicating its widespread expression in GC. A high Trop-2 expression level, characterized by an elevated H-score, was significantly associated with intestinal type by Lauren classification, gastric mucin type, presence of lymph node metastasis, human epidermal growth factor receptor 2-positivity, and Epstein-Barr virus (EBV)-positivity. Patients with a high Trop-2 expression level exhibited poorer survival outcomes on univariate and multivariate analyses. High EpCAM expression levels were prevalent in differentiated histologic type, microsatellite instability-high, and EBV-negative cancer, and were correlated with high densities of CD3 and CD8 T cells and elevated combined positive score for programmed death-ligand 1.

Conclusions: These results highlight the differential expression of Trop-2 and EpCAM and their prognostic implications in GC. The use of meticulously validated antibodies ensured the reliability of our IHC data, thereby offering a robust foundation for future therapeutic strategies targeting Trop family members in GC.