Spatial expression of claudin 18.2 in matched primaries and metastases of tubo-ovarian carcinoma of all subtypes

Wagner P, Gaß P, Pöschke P, Eckstein M, Gloßner L, Hartmann A, Beckmann M, Fasching P, Rübner M, Emons J, Erber R (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

Virchows Archiv Springer Verlag (Germany)

DOI: 10.1007/s00428-024-03756-1

Abstract

Physiologically, claudin 18 splice variant 2 (CLDN18.2) expression is restricted to the gastric epithelium, but its expression has been detected in solid cancers. Zolbetuximab, a chimeric IgG1 antibody targeting CLDN18.2, has demonstrated promising effects in patients suffering from CLDN18.2-positive, HER2-negative locally advanced gastric cancer and is currently being studied further. To date, little is known about CLDN18.2 expression in other histological subtypes of tubo-ovarian carcinoma (TOC) and their matching metastases. Using a cohort of all histological TOC subtypes, we investigated the immunohistochemical (IHC) CLDN18.2 expression in both TOCs (n = 536), their matching metastatic tissue (n = 385) and in 93 metastases without primary. Tissue microarrays comprised both the tumor center and periphery. IHC positivity was defined as biomarker expression of ≥ 75% in tumor cells with moderate-to-strong membranous staining. Overall CLDN18.2 positivity was 4.1% (21/515) in the TOC centers and 3.6% (18/498) in their peripheries. In primaries of mucinous tubo-ovarian carcinoma (MTOC), CLDN18.2 positivity rates were 45% (18/40) and 36.6% (15/41), respectively. Positivity rates for the corresponding metastases were 33% (4/12, center) and 27% (3/11, periphery). The expression was relatively homogenous throughout all tumor sites. With no expression in 99.5% of nonmucinous tumors, CLDN18.2 positivity was almost exclusively seen in the mucinous subtype. In tubo-ovarian carcinoma, CLDN18.2 expression was, with rare exceptions, restricted to the mucinous subtype. Among them, 33% of metastasized MTOCs presented with CLDN18.2 positivity. Hence, CLDN18.2 might display a promising target for personalized therapy in patients with advanced MTOC.

Authors with CRIS profile

Paul Wagner Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Paul Gaß Department of Obstetrics and Gynaecology Patrik Pöschke Department of Obstetrics and Gynaecology Markus Eckstein Institute of Pathology Laura Gloßner Medizinische Fakultät Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Matthias Beckmann Lehrstuhl für Geburtshilfe und Frauenheilkunde Peter Fasching Professur für Translationale Frauenheilkunde und Geburtshilfe Matthias Rübner Department of Obstetrics and Gynaecology Ramona Erber Institute of Pathology

How to cite

APA:

Wagner, P., Gaß, P., Pöschke, P., Eckstein, M., Gloßner, L., Hartmann, A.,... Erber, R. (2024). Spatial expression of claudin 18.2 in matched primaries and metastases of tubo-ovarian carcinoma of all subtypes. Virchows Archiv. https://doi.org/10.1007/s00428-024-03756-1

MLA:

Wagner, Paul, et al. "Spatial expression of claudin 18.2 in matched primaries and metastases of tubo-ovarian carcinoma of all subtypes." Virchows Archiv (2024).

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