Low Expression of Cell Adhesion Molecule 1 in Resected Gastroenteropancreatic Neuroendocrine Tumors: Relationship With Lymph Node and Distant Metastasis

Gastroenteropancreatic neuroendocrine tumors (GEP‐NETs) are clinically heterogeneous, making prediction of metastatic behavior challenging. This study examined Cell Adhesion Molecule 1 (CADM1) and the differentially expressed in adenocarcinoma of the lung‐1 expression in 75 resected GEP‐NETs and evaluated their associations with clinicopathological features, tumor grade, and established adhesion‐ or prognosis‐related markers, including E‐cadherin (ECAD), CD56, progesterone receptor (PgR), and cytokeratin 19 (CK19). CADM1 promoter methylation was assessed using methylation‐specific PCR, and the miR‐214 and miR‐375 expressions were analyzed by quantitative real‐time PCR. The expression of CADM1 was significantly lower in tumors with lymph node and/or distant metastasis ( p = 0.01), and a low CADM1 expression was independently associated with metastatic disease ( p = 0.0004; OR = 4.63). Additionally, low PgR ( p = 0.014; OR = 4.13) and a high CK19 ( p = 0.0002; OR = 4.83) expression, as reported previously, were linked to poor outcomes. In contrast, neither ECAD nor CD56 showed any notable associations with aggressive features in a univariable assessment. No significant relationship was observed between CADM1 promoter methylation and the CADM1 expression. These findings suggest that a reduced CADM1 expression may be associated with lymph node and distant metastasis in GEP‐NETs and could be a potential prognostic marker.