HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jonkers, Y M H Articles by Speel, E J M Search for Related Content PubMed PubMed Citation Articles by Jonkers, Y M H Articles by Speel, E J M

Department of Molecular Cell Biology (Box 17), Research Institute for Growth and Development (GROW), University of Maastricht, PO Box 616, 6200 MD Maastricht, The Netherlands
¹ Department of Pathology, Klinikum Rechts der Isar, 81675 Munzh, Germany
² Departments of Pathology, Stadtspital Triemli, CH-8023 Zurich, Switzerland
³ Department of Internal Medicine, section of Endocrinology and
⁴ Department of Pathology Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
⁵ Departments of Pathology and
⁶ Endocrinology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands
⁷ Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
⁸ Department of Medical Sciences, University Hospital Uppsala, Uppsala, Sweden
⁹ Department of Clinical and Biological Sciences, University of Turin and San Luigi Hospital, Orbassano-Torino, Italy
¹⁰ Department of Epidemiology, University of Maastricht, Maastricht, The Netherlands

(Correspondence should be addressed to Y M H Jonkers; Email: y.jonkers{at}molcelb.unimaas.nl)

The clinical behavior of endocrine pancreatic tumors (EPTs) is difficult to predict in the absence of metastases or invasion to adjacent organs. Several markers have been indicated as potential predictors of metastatic disease, such as tumor size 2 cm, Ki67 proliferative index 2%, cytokeratin (CK) 19 status, and recently in insulinomas, chromosomal instability (CIN). The goal of this study was to evaluate the value of these markers, and in particular of the CIN, to predict tumor recurrence or progression and tumor-specific death, using a series of 47 insulinomas and 24 non-insulinoma EPTs. From these EPT cases, a genomic profile has been generated and follow-up data have been obtained. The proliferative index has been determined in 68 tumors and a CK19 expression pattern in 50 tumors. Results are statistically analyzed using Kaplan–Meier plots and the log-rank statistic. General CIN, as well as specific chromosomal alterations such as 3p and 6q loss and 12q gain, turned out to be the most powerful indicators for poor tumor-free survival (P0.0004) and tumor-specific death (P0.0113) in insulinomas. The CIN, chromosome 7q gain, and a proliferative index 2% were reliable in predicting a poor tumor-free survival in non-insulinoma EPTs (P0.0181, whereas CK19 expression was the most optimal predictor of tumor-specific death in these tumors. In conclusion, DNA copy number status is the most sensitive and efficient marker of adverse clinical outcome in insulinomas and of potential interest in non-insulinoma EPTs. As a consequence, this marker should be considered as a prognosticator to improve clinical diagnosis, most practically as a simple multi-target test.

This article has been cited by other articles:

				S. Pizzi, C. Azzoni, E. Tamburini, L. Bottarelli, N. Campanini, T. D'Adda, G. Fellegara, T. V. Luong, C. Pasquali, G. Rossi, et al. Adenomatous polyposis coli alteration in digestive endocrine tumours: correlation with nuclear translocation of {beta}-catenin and chromosomal instability Endocr. Relat. Cancer, December 1, 2008; 15(4): 1013 - 1024. [Abstract] [Full Text] [PDF]