Allelotyping analysis of GEP endocrine tumors
Department of Clinical and Biological Sciences, University of Insubria, Varese, Italy
AIM: The molecular pathogenesis of GEP endocrine tumors is still largely unknown and no specific prognostic molecular markers have been yet identified. The purpose of this work was to identify specific chromosome regions or putative tumor suppressor loci that may be involved in the malignant evolution of these tumors. METHODS: 24 well differentiated endocrine tumors (WDETs) (11 pancreatic, 3 gastric, 10 intestinal) and 14 poorly differentiated endocrine carcinomas (PDECs) (1 pancreatic, 6 gastric, 7 colorectal) were allelotyped with an automated DNA sequencer (Applied Biosystems 310) using 38 polymorphic microsatellite markers covering chromosomes 1, 3, 5q, 6, 11, 17 and 18. RESULTS: Regardless of the primary site, a significantly higher percentage of allelic imbalances (AI) was observed in PDECs than in WDETs (p= 0.012) with the only exception for 3 out of 8 nonfunctioning pancreatic tumors exhibiting multiple AI on chromosomes 11, 6q and 3p. A strong positive correlation between AI percentage and the Ki-67 proliferation index was detected considering both all tumors and WDETs alone (p=0.002 and p=0.001, respectively). Moreover, AI at 17p was the most frequent alteration observed in PDECs (92% of PDECs versus 4.8% of WDETs; p<0.01) together with 6q and 3p AI in gastric and 5q AI in colorectal PDECs, respectively. CONCLUSIONS: These findings suggest the existence of two different molecular profiles associated with PDECs and WDETs. Since no specific molecular markers of malignancy can be defined with certainty, the ploidy status and the evaluation of the global level of chromosomal instability of the tumors appear to be the most informative genetic factors with prognostic significance.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 893 (Molecular pathology).