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

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Názov: Spatial expression of claudin 18.2 in matched primaries and metastases of tubo-ovarian carcinoma of all subtypes
Autori: Paul Wagner, Paul Gass, Patrik Pöschke, Markus Eckstein, Laura Gloßner, Arndt Hartmann, Matthias Wilhelm Beckmann, Peter Andreas Fasching, Matthias Ruebner, Julius Emons, Ramona Erber
Zdroj: Virchows Arch
Informácie o vydavateľovi: Springer Science and Business Media LLC, 2024.
Rok vydania: 2024
Predmety: Ovarian Neoplasms, 0301 basic medicine, Middle Aged, Immunohistochemistry, 03 medical and health sciences, 0302 clinical medicine, Fallopian Tube Neoplasms/metabolism [MeSH], Female [MeSH], CLDN18.2, Mucinous tubo-ovarian carcinoma, Aged [MeSH], Humans [MeSH], Tubo-ovarian cancer, Middle Aged [MeSH], Tissue Array Analysis [MeSH], Fallopian Tube Neoplasms/pathology [MeSH], Ovarian Neoplasms/metabolism [MeSH], Immunohistochemistry [MeSH], Original Article, Claudins/analysis [MeSH], Targeted therapy, Biomarkers, Tumor/analysis [MeSH], Claudins/metabolism [MeSH], Ovarian Neoplasms/pathology [MeSH], Tissue Array Analysis, Claudins, Biomarkers, Tumor, Humans, Fallopian Tube Neoplasms, Female, Aged
Popis: 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.
Druh dokumentu: Article
Other literature type
Jazyk: English
ISSN: 1432-2307
0945-6317
DOI: 10.1007/s00428-024-03756-1
Prístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/38326579
https://repository.publisso.de/resource/frl:6492559
Rights: CC BY
Prístupové číslo: edsair.doi.dedup.....cca2c04e732ae4ea0db47cd5e8e43455
Databáza: OpenAIRE
Popis
Abstrakt: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.
ISSN:14322307
09456317
DOI:10.1007/s00428-024-03756-1