Chromosome 3p alterations in pancreatic endocrine neoplasia

Abstract

Pancreatic endocrine tumors (PET) are rare neoplasms classified as functioning (F-PET) or non-functioning (NF-PET) according to the presence of a clinical syndrome due to hormonal hypersecretion. PETs show variable degrees of clinical aggressiveness and loss of chromosome 3p has been suggested to be associated with an advanced stage of disease. We assessed chromosome 3p copy number in 113 primary PETs and 32 metastases by fluorescence in situ hybridization (FISH) using tissue microarrays. The series included 56 well-differentiated endocrine tumors (WDET), 62 well-differentiated endocrine carcinomas (WDEC), and 6 poorly differentiated endocrine carcinomas (PDEC). Chromosome 3p alterations were found in 23/113 (20%) primary tumors, with losses being predominant over gains (14% vs. 6%). Loss of 3p was found in 5/55 (9%) WDET, 11/52 (21%) WDEC, and never in PDEC. Gains of 3p were detected in 4/55 (7%) WDET, no WDEC, but notably in 3/6 (50%) PDEC (OR 23.6; P = 0.003). Metastases were more frequently monosomic for 3p compared to primary tumors (OR 3.6; P = 0.005). Monosomy was significantly associated with larger tumor size, more advanced tumor stage, and metastasis. No association was found with survival. Chromosome 3p copy number alterations are frequent events in advanced stage PET, with gains prevailing in PDEC while losses are more frequent in WDEC, supporting the view that a specific pattern of alterations are involved in these diverse disease subtypes.