Universität zu Köln

Pak, Svetlana, Simon, Adrian Georg ORCID: 0000-0002-2709-863X, Lyu, Su Ir ORCID: 0009-0002-4125-6048, Tolkach, Yuri ORCID: 0000-0001-5239-2841, Alakus, Hakan ORCID: 0000-0002-3889-3276, Zander, Thomas ORCID: 0000-0002-4266-6818, Buettner, Reinhard ORCID: 0000-0001-8806-4786, Bruns, Christiane Josephine ORCID: 0000-0001-6590-8181, Schroeder, Wolfgang ORCID: 0000-0002-8700-069X and Quaas, Alexander ORCID: 0000-0002-3537-6011 (2025). The expression of the tight junction protein and therapeutical target Claudin 18.2 is heterogeneously distributed within esophageal and gastric adenocarcinoma. Scientific Reports, 15 (1). pp. 1-11. Springer Nature. ISSN 2045-2322

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Abstract

[Artikel-Nr.: 28958] Claudin 18.2 (CLDN18.2) is a therapeutically relevant biomarker in esophageal (EAC) -and gastric adenocarcinoma (GAC). Little is known about its heterogeneity within the primary tumor and corresponding metastases and how many biopsies are needed to determine the true CLDN18.2 status of a tumor. CLDN18.2 was assessed in 1,283 patients (822 EAC, 461 GAC), using the antibody clone 43–14 A. Eight virtual endoscopic biopsies were taken from digitized whole tumor blocks. 204 of 822 EAC (24.8%) and 132 of 461 GAC (28,6%) were positive for CLDN18.2. In GAC, CLDN18.2 expression showed a trend towards less invasive growth ( p = 0.02) and less common lymph node metastasis ( p = 0.07) and was more often observed within the EBV-associated subtype ( p = 0.01). When comparing the expression in one biopsy with the whole tissue section, the sensitivity for CLDN18.2 was low (58.8%). The sensitivity increased to a maximum of 76.5% with 6 and 8 biopsies (positive likelihood ratio = 17.8). Discordant expression between primary tumor and corresponding local lymph node metastasis was observed in 18.5%. This study highlights that CLDN18.2 is a heterogeneously expressed biomarker, within the tumor tissue as well as in primary tumor and corresponding lymph node metastasis. In case of CLN18.2-negative results the representativity of the biopsies must be critically assessed and a re-biopsy might be recommendable.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Pak, Svetlana UNSPECIFIED UNSPECIFIED UNSPECIFIED Simon, Adrian Georg UNSPECIFIED https://orcid.org/0000-0002-2709-863X UNSPECIFIED Lyu, Su Ir UNSPECIFIED https://orcid.org/0009-0002-4125-6048 UNSPECIFIED Tolkach, Yuri UNSPECIFIED https://orcid.org/0000-0001-5239-2841 UNSPECIFIED Alakus, Hakan UNSPECIFIED https://orcid.org/0000-0002-3889-3276 UNSPECIFIED Zander, Thomas UNSPECIFIED https://orcid.org/0000-0002-4266-6818 UNSPECIFIED Buettner, Reinhard UNSPECIFIED https://orcid.org/0000-0001-8806-4786 UNSPECIFIED Bruns, Christiane Josephine UNSPECIFIED https://orcid.org/0000-0001-6590-8181 UNSPECIFIED Schroeder, Wolfgang UNSPECIFIED https://orcid.org/0000-0002-8700-069X UNSPECIFIED Quaas, Alexander UNSPECIFIED https://orcid.org/0000-0002-3537-6011 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-809583
Identification Number:	10.1038/s41598-025-12337-4
Journal or Publication Title:	Scientific Reports
Volume:	15
Number:	1
Page Range:	pp. 1-11
Number of Pages:	11
Date:	7 August 2025
Publisher:	Springer Nature
ISSN:	2045-2322
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Anästhesiologie und Operative Intensivmedizin > Klinik für Anästhesiologie und Operative Intensivmedizin Faculty of Medicine > Chirurgie > Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Transplantationschirurgie Faculty of Medicine > Pathologie und Neuropathologie > Institut für Pathologie
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Esophageal cancer ; Zolbetuximab ; Claudin ; Tight junctions ; Gastric cancer English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/80958