Alterations of chromosome 3p in 24 cases of gastrinomas and their correlations with clinicopathological and prognostic features

Abstract

Abstract Purpose: The pathogenesis of gastrinomas is largely unknown, and there is a lack of reliable genetic determinants that are useful to distinguish malignant and benign forms of this tumor or predict the prognosis of patients with this disease. Loss of heterozygosity (LOH) on chromosome 3p is reported to occur in pancreatic neuroendocrine tumors (PNETs) as well as in non-PNETs and its presence is reported to correlate with tumor prognosis in non-endocrine tumors. However, little data are available from prospective studies on gastrinomas. Experimental design: We assessed occurrence of 3p LOH in 24 gastrinomas and correlated its presence with tumor biological behavior and other clinicopathological features of gastrinomas. Results: Either 3p LOH or microsatellite instability involving 3p occurred in 11 of 24 tumors (46%). Seven (29%) gastrinomas had 3p LOH. Of the 7 gastrinomas with 3p LOH, 5 (71%) had 3p12 LOH with the marker D3S2406, which was the shortest region of highest overlap (SRO). Chromosome 3p LOH was not associated with aggressive biological behavior of gastrinomas or with poor prognosis of patients with gastrinoma. Similarly, 3p12 LOH (SRO) was not correlated with aggressive growth of tumors and/or liver metastases. Conclusion: Gastrinomas have a relative high frequency of 3p12 LOH suggesting this area may harbor putative tumor suppressor gene(s), which may play a role in the tumorigenesis, but not aggressiveness, of a subset of these tumors.