Chromosomal instability predicts metastatic disease in patients with insulinomas.

Y.M.H. Jonkers, S.M.H. Claessen, A. Perren, S. Schmid, P. Komminoth, A.A. Verhofstad, L.J. Hofland, R.R. de Krijger, P.J. Slootweg, F.C.S. Ramaekers, E.J.M. Speel

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Endocrine pancreatic tumors (EPTs) comprise a highly heterogeneous group of tumors with different clinical behavior and genetic makeup. Insulinomas represent the predominant syndromic subtype of EPTs. The metastatic potential of insulinomas can frequently not be predicted using histopathological criteria, and also molecular markers indicating malignant progression are unreliable because of the small number of cases per subtype studied so far. For the identification of reliable indicators of metastatic disease, we investigated 62 sporadic insulinomas (44 benign and 18 tumors with metastases) by means of comparative genomic hybridization (CGH). In addition, the role of MEN1 (multiple endocrine neoplasia type 1) gene mutations was determined to assess specific chromosomal alterations associated with dysfunction of this endocrine tumor-related tumor suppressor gene. Only one case with a somatic MEN1 mutation was identified (1527del7bp), indicating that the MEN1 gene plays a minor pathogenic role in sporadic insulinomas. CGH analysis revealed that the total number of aberrations per tumor differs strongly between the benign and the malignant group (4.2 vs 14.1; P<>= 8, rather than parameters such as tumor size and proliferation index, is the most powerful indicator for the development of metastatic disease in patients with sporadic insulinoma.
Original languageEnglish
Pages (from-to)435-447
JournalEndocrine-Related Cancer
Publication statusPublished - 1 Jan 2005

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Jonkers, Y. M. H., Claessen, S. M. H., Perren, A., Schmid, S., Komminoth, P., Verhofstad, A. A., Hofland, L. J., de Krijger, R. R., Slootweg, P. J., Ramaekers, F. C. S., & Speel, E. J. M. (2005). Chromosomal instability predicts metastatic disease in patients with insulinomas. Endocrine-Related Cancer, 12, 435-447.