| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Molecular Cell Biology (Box 17), Research Institute for Growth and Development, University of Maastricht, PO Box 616, 6200 MD, Maastricht, The Netherlands
1 Department of Pathology, University Hospital, Zurich, Switzerland
2 Department of Pathology, Hospital Baden, Switzerland
3 Department of Pathology, University Medical Center, Nijmegen, The Netherlands
4 Department of Internal Medicine, University Medical Center, Rotterdam, The Netherlands
5 Department of Pathology, University Medical Center, Rotterdam, The Netherlands
6 Department of Pathology, University Medical Center, Utrecht, The Netherlands
(Requests for offprints should be addressed to Y M H Jonkers; Email: Y.Jonkers{at}MOLCELB.unimaas.nl)
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<0.0001). Furthermore, chromosome 9q gain was found to be the most frequent aberration in both benign and malignant insulinomas, whereas chromosome 6q losses and 12q, 14q and 17pq gains are strongly associated with metastatic disease. Our study shows that chromosomal instability, as defined by
5 gains together with 5 losses, or total number of gains and losses 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.
This article has been cited by other articles:
|
|
 |
|
  T. R Halfdanarson, J. Rubin, M. B Farnell, C. S Grant, and G. M Petersen Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors Endocr. Relat. Cancer, June 1, 2008; 15(2): 409 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V. de Sa, M. L. Correa-Giannella, M. C. Machado, K. Krogh, M. Q. de Almeida, M. A. Albergaria Pereira, S. A. Coelho Siqueira, R. A. Patzina, F. S. Ibuki, M. C. Sogayar, et al. Serpin Peptidase Inhibitor Clade A Member 1 as a Potential Marker for Malignancy in Insulinomas Clin. Cancer Res., September 15, 2007; 13(18): 5322 - 5330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y M H Jonkers, S M H Claessen, A Perren, A M Schmitt, L J Hofland, W de Herder, R R de Krijger, A A J Verhofstad, A R Hermus, J A Kummer, et al. DNA copy number status is a powerful predictor of poor survival in endocrine pancreatic tumor patients Endocr. Relat. Cancer, September 1, 2007; 14(3): 769 - 779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Gocheva, W. Zeng, D. Ke, D. Klimstra, T. Reinheckel, C. Peters, D. Hanahan, and J. A. Joyce Distinct roles for cysteine cathepsin genes in multistage tumorigenesis Genes & Dev., March 1, 2006; 20(5): 543 - 556. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
