High resolution allelotype of nonfunctional pancreatic endocrine tumors: Identification of two molecular subgroups with clinical implications

A high resolution allelotype for nonfunctional pancreatic endocrine tumors (NF-PETs) has been generated by microsatellite analysis of DNA from 16 froz en cases, each probed with 394 markers. Two subgroups of NF-PETs were found . Seven cases showed frequent, large allelic deletions [loss of heterozygos ity (LOH)] with an average fractional allelic loss (FAL) of 0.55, whereas n ine cases showed a small number of random losses with a FAL of 0.15. Design ated high or low FAL, respectively, these genetic phenotypes showed correla tion with the ploidy status: high-FAL tumors were aneuploid, low-FAL were d iploid. Chromosomes 6q and 11q showed LOH in >60% of cases. About 50% of ca ses had losses on 11p, 20q, and 21. Selected LOH analysis on an additional 16 paraffin-embedded NF-PETs confirmed the high frequency of 6q and 11q LOH . The allelotype of NF-PET is markedly different from that of either ductal or acinar tumors of the pancreas as web as from that of functional PETs. M oreover, whereas deletions involving chromosome 11 also are a feature of fu nctional-PETs. the involvement of chromosome 6q is characteristic of NF-PET s. Survival analysis showed that none of the single chromosomal alterations was associated with outcome, whereas ploidy status is an independent facto r adding prognostic information to that furnished by the proliferative inde x measured by Ki-67 immunohistochemistry.