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

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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.

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