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Fetal gut cell-like differentiation in esophageal adenocarcinoma defines a rare tumor subtype with therapeutically relevant claudin-6 positivity and SWI/SNF gene alteration.
- Source :
-
Scientific reports [Sci Rep] 2024 Jun 12; Vol. 14 (1), pp. 13474. Date of Electronic Publication: 2024 Jun 12. - Publication Year :
- 2024
-
Abstract
- Esophageal adenocarcinoma (EAC) is one of the deadliest tumor entities worldwide, with a 5-year survival rate of less than 25%. Unlike other tumor entities, personalized therapy options are rare, partly due to the lack of knowledge about specific subgroups. In this publication, we demonstrate a subgroup of patients with EAC in a large screening cohort of 826 patients, characterized by specific morphological and immunohistochemical features. This subgroup represents approximately 0.7% (6/826) of the total cohort. Morphological features of this subgroup show a striking clear cytoplasm of the tumour cells and the parallel existence of rare growth patterns like yolk sac-like differentiation and enteroblastic differentiation. Immunohistochemistry reveals expression of the fetal gut cell-like proteins Sal-like protein 4 (SALL4), claudin-6, and glypican 3. Interestingly, we find a correlation with alterations of SWI/SNF-complex associated genes, which are supposed to serve as tumor suppressor genes in various tumour entities. Our results suggest a possible implication of rare tumour subtypes in the WHO classification for EACs according to the classification for gastric cancer. Furthermore, claudin-6 positive tumors have shown promising efficacy of CAR T cell therapy in the recently published BNT-211-01 trial (NCT04503278). This represents a personalized therapeutic option for this tumor subtype.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Female
Male
Aged
Claudins metabolism
Claudins genetics
Middle Aged
Biomarkers, Tumor metabolism
Biomarkers, Tumor genetics
Esophageal Neoplasms metabolism
Esophageal Neoplasms genetics
Esophageal Neoplasms pathology
Adenocarcinoma metabolism
Adenocarcinoma genetics
Adenocarcinoma pathology
Cell Differentiation
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 38866822
- Full Text :
- https://doi.org/10.1038/s41598-024-64116-2