Concordance of claudin-18.2 expression in biopsy, resection, and recurrent specimens: implications for zolbetuximab therapy in pancreatic ductal adenocarcinoma DOI
Daisuke Kyuno,

Kazuhiko Yanazume,

Akira Saitō

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

ABSTRACT Claudin-18.2 is a promising therapeutic target for gastrointestinal cancer. However, its expression pattern in pancreatic ductal adenocarcinoma, especially the concordance between biopsy and resection specimens, unknown. This study aimed to evaluate consistency of claudin-18.2 positivity across different specimen types using clinically validated antibody clone 43-14A employed ongoing zolbetuximab trials. Immunohistochemical analysis claudin-18 was conducted on 211 resected cancer tissues, 133 matched preoperative samples, 60 samples from recurrent lesions. Concordance rates were calculated based relevant cutoff (≥75% tumor cells with moderate-to-strong membranous staining). Receiver operating characteristic used optimize thresholds. observed 9.5% specimens. The 92.5% specimens 83.3% primary suggested that lower (20%) achieved 100% sensitivity detecting positive cases. While overall levels maintained most lesions, decreased frequently cases local recurrence liver metastasis. Despite intrinsic heterogeneity limited yield cancer, small assessed clinical trial-validated 43-14A, strongly correlated These results suggest stable biomarker therapy patients adenocarcinoma. Graphical abstract Core Tips demonstrated high (92.5%) CLDN18.2 adenocarcinoma 43-14A. lesions generally remained consistent corresponding tumor, although reduction metastases. findings support utility biopsy-based evaluation selecting who may benefit zolbetuximab.

Language: Английский

Concordance of claudin-18.2 expression in biopsy, resection, and recurrent specimens: implications for zolbetuximab therapy in pancreatic ductal adenocarcinoma DOI
Daisuke Kyuno,

Kazuhiko Yanazume,

Akira Saitō

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

ABSTRACT Claudin-18.2 is a promising therapeutic target for gastrointestinal cancer. However, its expression pattern in pancreatic ductal adenocarcinoma, especially the concordance between biopsy and resection specimens, unknown. This study aimed to evaluate consistency of claudin-18.2 positivity across different specimen types using clinically validated antibody clone 43-14A employed ongoing zolbetuximab trials. Immunohistochemical analysis claudin-18 was conducted on 211 resected cancer tissues, 133 matched preoperative samples, 60 samples from recurrent lesions. Concordance rates were calculated based relevant cutoff (≥75% tumor cells with moderate-to-strong membranous staining). Receiver operating characteristic used optimize thresholds. observed 9.5% specimens. The 92.5% specimens 83.3% primary suggested that lower (20%) achieved 100% sensitivity detecting positive cases. While overall levels maintained most lesions, decreased frequently cases local recurrence liver metastasis. Despite intrinsic heterogeneity limited yield cancer, small assessed clinical trial-validated 43-14A, strongly correlated These results suggest stable biomarker therapy patients adenocarcinoma. Graphical abstract Core Tips demonstrated high (92.5%) CLDN18.2 adenocarcinoma 43-14A. lesions generally remained consistent corresponding tumor, although reduction metastases. findings support utility biopsy-based evaluation selecting who may benefit zolbetuximab.

Language: Английский

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