Alterations of E-cadherin, α-catenin and β-catenin expression in neuroendocrine tumors of the gastrointestinal tract

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Abstract
Neuroendocrine tumors (NETs) of the gastrointestinal tract comprise a heterogeneous group of neoplasms arising from the diffuse neuroendocrine system. These tumors strongly differ from each other on the basis of different pathogenetic, clinical, functional, histological, and prognostic patterns. Previous studies have shown that abnormal and reduced expression of the E-cadherin/catenin complex in several human cancers is associated with tumor dedifferentiation, advanced clinical stages, and poor survival rate. We assessed correlations between the expression of E-cadherin and catenins, Ki-67, and the following clinicopathological factors: age, embryological site of origin, size, histological growth pattern, the depth of penetration into the intestinal wall, and the presence of metastasis. In this study, reduction of membranous E-cadherin expression to a variable degree was detected in more than two-thirds (42 of 51) of gastrointestinal NETs (19 foregut, 8 midgut, and 24 hindgut) belonging to the complete neuroendocrine neoplastic spectrum [18 well-differentiated NETs, 22 well-differentiated neuroendocrine carcinomas (NECs), and 11 poorly differentiated NECs]. The reduction of E-cadherin expression was concomitant with the reduction of α-catenin (44 of 51) and β-catenin (35 of 51) expression. Our immunohistochemical analysis demonstrated significant differences of percentage of membranous positive cells of E-cadherin, α-catenin, or β-catenin between normal tissues and well-differentiated NETs (P=0.0038, P=0.004, and P=0.0329, respectively), well-differentiated NECs (P P PP=0.0002, P P=0.0002, respectively). Among the gastrointestinal NETs, there were significantly more positive cells of E-cadherin, α-catenin, or β-catenin in well-differentiated NETs than well-differentiated NECs (P=0.0006, P=0.0065, and P=0.0001, respectively) or poorly differentiated NECs (P=0.0053, P=0.0041, and PP PP P=0.0001, and PP=0.0013, P=0.0001, and P<0.0001, respectively). These results indicate that the alteration in the E-cadherin/catenin expression may be involved in the growth and progression of gastrointestinal NETs.

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