High frequency of down-regulation of E-cadherin detected in benign sporadic insulinomas by multiplex ligation-dependent probe amplification

SummaryInsulinomas are the most common functioning pancreatic endocrine tumors, and the previous studies showed that the chromosomal aberrations of Chr.9q, 11q, and 22q were associated with the development and progression of insulinoma. To analyze the genetic alterations in sporadic insulinoma, we tested 23 tumor samples using multiplex ligation-dependent probe amplification. The results showed that 20 (87%) of the 23 patients had lost CDH1, a tumor suppressor gene. Immunofluorescence analysis of the E-cadherin and β-catenin proteins further confirmed the impaired expression of E-cadherin and the translocation of β-catenin in sporadic insulinomas. It was found that the cytoplasmic accumulation of β-catenin coincided with the decrease or loss of E-cadherin synthesis during the tumorigenesis of sporadic insulinomas. Our study suggests that the inactivation of CDH1 is an important and early event in the development of these tumor types.