Publications

Authors:

Angerilli, Valentina; Callegarin, Matilde; Govoni, Ilaria; De Lisi, Giuseppe; Paudice, Michele; Fugazzola, Paola; Vanoli, Alessandro; Parente, Paola; Bergamo, Francesca; Luchini, Claudio; Dei Tos, Angelo Paolo; Grillo, Federica; Lonardi, Sara; Mastracci, Luca; Spolverato, Gaya; Fassan, Matteo

Title:

Heterogeneity of predictive biomarker expression in gastric and esophago-gastric junction carcinoma with peritoneal dissemination

Year:

2025

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

No

Name of journal:

Gastric Cancer

ISSN of journal:

1436-3291

N° Volume:

Online ahead of print

Number or Folder:

Apr 9

Page numbers:

1-10

Keyword:

Biomarkers; Gastroesophageal cancer; Heterogeneity; Targeted therapy

Short description of contents:

Background: Temporal and spatial molecular heterogeneity contributes to resistance to targeted and immune therapies in gastric and esophagogastric junction carcinoma (G/EGJ). This study evaluates differences in biomarker expression between primary G/EGJ and paired peritoneal metastases (PM). Methods: We analyzed 74 cases of primary G/EGJ and paired PM using immunohistochemistry for HER2, PD-L1, Claudin18 (CLDN18), DNA mismatch repair (MMR) proteins, p53, E-cadherin, and in situ hybridization for EBER. Biomarker concordance between primary and metastatic tumors was assessed. Results: Primary G/EGJ were predominantly poorly cohesive (45.9%) or mixed-type (37.8%). Regarding predictive biomarkers, low rates of HER2 overexpression (5.4%), MMR deficiency (4.1%), and EBER positivity (1.4%) were observed, while PD-L1 CPS ≥ 1 occurred in 79.7% of cases and CLDN18 positivity was observed in 31.1% of cases. Concordance was perfect for MMR and EBER, while PD-L1 showed the highest discordance (32.4%). HER2 had a low discordance rate (2.7%). CLDN18 exhibited good concordance (86.5%) and showed consistent positivity in PD-L1- and HER2-negative primary tumors (28.6%). Conclusion: G/EGJ with PM show distinct molecular features and spatial heterogeneity, with MMR, EBER, and HER2 demonstrating strong concordance, while PD-L1 showed greater variability. As for novel biomarkers, CLDN18.2 shows substantial concordance between primary G/EGJ and PM and could be a promising target in HER2/PD-L1-negative G/EGJ with PM.

Product ID:

145189

Handle IRIS:

11562/1159839

Last Modified:

April 25, 2025

Bibliographic citation:

Angerilli, Valentina; Callegarin, Matilde; Govoni, Ilaria; De Lisi, Giuseppe; Paudice, Michele; Fugazzola, Paola; Vanoli, Alessandro; Parente, Paola; Bergamo, Francesca; Luchini, Claudio; Dei Tos, Angelo Paolo; Grillo, Federica; Lonardi, Sara; Mastracci, Luca; Spolverato, Gaya; Fassan, Matteo, Heterogeneity of predictive biomarker expression in gastric and esophago-gastric junction carcinoma with peritoneal dissemination «Gastric Cancer» , vol. Online ahead of print , n. Apr 9 , 2025 , pp. 1-10

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