Publications

Authors:

Angerilli, V; Sacchi, D; Rizzato, M; Gasparello, J; Ceccon, C; Sabbadin, M; Niero, M; Bergamo, F; Cillo, U; Franzina, C; Luchini, C; Dei Tos, A P; Lonardi, S; Fassan, M

Title:

Claudin 18.2: a promising actionable target in biliary tract cancers

Year:

2025

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

No

Name of journal:

ESMO OPEN

ISSN of journal:

2059-7029

N° Volume:

10

Number or Folder:

5

Page numbers:

1-7

Keyword:

CLDN18.2; biliary tract cancer; cholangiocarcinoma; claudin 18.2; gallbladder carcinoma; immunohistochemistry

Short description of contents:

Background and purpose: Anti-claudin 18.2 (anti-CLDN18.2) therapy has been approved for patients with CLDN18-positive gastric and gastroesophageal junction adenocarcinomas. The current study aims at evaluating the expression of CLDN18 in a large cohort of pathologically characterized biliary tract cancers (BTCs). Materials and methods: A series of 237 BTCs were collected and reviewed under the BITCOIN protocol. All samples were assessed for CLDN18 status using immunohistochemistry (clone 43-14A). Tumor positivity for CLDN18 was determined if ≥75% of tumor cells exhibited moderate-to-strong membranous staining. Results: CLDN18 expression was found in 29.5% of BTCs (70/237), with the highest rates in gallbladder carcinoma (GBC; 62.5%; 20/32) and extrahepatic cholangiocarcinoma (eCCA; 53.4%; 31/58), compared with intrahepatic cholangiocarcinoma (iCCA; 12.9%; 19/147) (P < 0.0001). CLDN18 positivity was detected in 5.5% of cases (13/237), most common in GBC (15.6%; 5/32), followed by eCCAs (8.6%; 5/58) and iCCAs (2.0%; 3/147) (P = 0.0045). Most CLDN18-positive samples (10/13) exhibited a heterogenous staining pattern. In iCCAs, large duct subtypes had higher CLDN18 expression [33.3% (10/30) versus 7.7% (9/117), P = 0.0002] and positivity [6.7% (2/30) versus 0.9% (1/117), P = 0.106] than small duct iCCAs. No significant differences were observed across GBC and eCCA histotypes, and CLDN18 was not associated with IDH1 or FGFR2 status in iCCAs. Conclusions: This study demonstrates that CLDN18 expression is present in a subset of BTCs, with significantly higher positivity rates in GBCs and eCCAs compared with iCCAs. In iCCAs, CLDN18 expression was more frequent in the large duct subtype but was not associated with IDH1 or FGFR2 status. These findings suggest that CLDN18 could be a potential therapeutic target in BTCs, warranting further prospective studies to evaluate its clinical significance and impact on patient outcomes.

Product ID:

145201

Handle IRIS:

11562/1159830

Last Modified:

May 16, 2025

Bibliographic citation:

Angerilli, V; Sacchi, D; Rizzato, M; Gasparello, J; Ceccon, C; Sabbadin, M; Niero, M; Bergamo, F; Cillo, U; Franzina, C; Luchini, C; Dei Tos, A P; Lonardi, S; Fassan, M, Claudin 18.2: a promising actionable target in biliary tract cancers «ESMO OPEN» , vol. 10 , n. 5 , 2025 , pp. 1-7

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo