Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas

Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas

The tight junction protein claudin-18 (CLDN18), is often expressed in various cancer types including gastric (GC) and gastroesophageal adenocarcinomas (GECs). In the last years, the isoform CLDN18.2 emerged as a potential drug target in metastatic GCs, leading to the development of monoclonal antibo...

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Autores principales: Antonio Pellino, Stefano Brignola, Erika Riello, Monia Niero, Sabina Murgioni, Maria Guido, Floriana Nappo, Gianluca Businello, Marta Sbaraglia, Francesca Bergamo, Gaya Spolverato, Salvatore Pucciarelli, Stefano Merigliano, Pierluigi Pilati, Francesco Cavallin, Stefano Realdon, Fabio Farinati, Angelo Paolo Dei Tos, Vittorina Zagonel, Sara Lonardi, Fotios Loupakis, Matteo Fassan
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
CLDN18.2
gastric adenocarcinoma
biomarkers
immunohistochemistry
Medicine
R
Acceso en línea:https://doaj.org/article/b46fe1fae9344ce2b6b50d9f95f3903c
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Sumario:The tight junction protein claudin-18 (CLDN18), is often expressed in various cancer types including gastric (GC) and gastroesophageal adenocarcinomas (GECs). In the last years, the isoform CLDN18.2 emerged as a potential drug target in metastatic GCs, leading to the development of monoclonal antibodies against this protein. CLDN18.2 is the dominant isoform of CLDN18 in normal gastric and gastric cancer tissues. In this work, we evaluated the immunohistochemical (IHC) profile of CLDN18 and its correlation with clinical and histopathological features including p53, E-cadherin, MSH2, MSH6, MLH1, PMS2, HER2, EBER and PD-L1 combined positive score, in a large real-world and mono-institutional series of advanced GCs (<i>n</i> = 280) and GECs (<i>n</i> = 70). The association of IHC results with survival outcomes was also investigated. High membranous CLDN18 expression (2+ and 3+ intensity ≥75%) was found in 117/350 (33.4%) samples analyzed. CLDN18 expression correlated with age <70 (<i>p</i> = 0.0035), positive EBV status (<i>p</i> = 0.002), high stage (III, IV) at diagnosis (<i>p</i> = 0.003), peritoneal involvement (<i>p</i> < 0.001) and lower incidence of liver metastases (<i>p</i> = 0.013). CLDN18 did not correlate with overall survival. The predictive value of response of CLDN18 to targeted agents is under investigation in several clinical trials and further studies will be needed to select patients who could benefit from these therapies.

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