Malignant effusions serve as a feasible source for therapy-related biomarker testing in advanced gastric cancer.

Abstract

Aims: Malignant effusion is a common manifestation of metastatic gastric cancer. This study compared the expression of key biomarkers (human epidermal growth factor receptor 2 (HER2), programmed cell death ligand 1 (PD-L1), claudin 18.2 (CLDN18.2) and fibroblast growth factor receptor 2b (FGFR2b)) between malignant effusion-derived cell blocks (CBs) and matched primary or metastatic tumour tissues and evaluated the longitudinal concordance of biomarker expression in serially collected CBs.

Methods: Biomarker status was retrospectively assessed by immunohistochemistry in CBs from malignant effusions and paired primary/metastatic gastric adenocarcinomas. HER2+ cases underwent fluorescence in situ hybridisation to confirm amplification.

Results: CLDN18.2 showed the highest positivity rate (34.0%). PD-L1 expression was positive in 8.6% of tumours and 13.9% of stroma. Lower rates were observed for FGFR2b (3.8%) and HER2 (3.3%). FGFR2b positivity was more frequent in CBs than in primary tumours (p=0.044) with higher expression levels (p=0.02). Conversely, CLDN18.2 positivity was lower in CBs versus primary tumours (p=0.004). Metastatic lesions showed higher CLDN18.2 positivity (p=0.04) and expression levels (p=0.002) compared with CBs. Serial CB analysis revealed high concordance rates: FGFR2b (99.1%), HER2 (98.1%), tumour PD-L1 (94.8%) and CLDN18.2 (92.2%).

Conclusions: Malignant effusion CBs show favourable intra-patient biomarker consistency over time, supporting their feasibility for longitudinal monitoring. Effusion-based testing shows potential value for potentially identifying candidates for FGFR2b-targeted therapies, pending further clinical validation.