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 > or =2 cm, Ki67 proliferative index > or =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 (P< or =0.0004) and
tumor-specific death (P< or =0.0113) in
insulinomas. The CIN, chromosome 7q gain, and a proliferative index > or =2% were reliable in predicting a poor
tumor-free survival in non-
insulinoma EPTs (P< or =0.0181, 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.