A characteristic of human gastroenteropancreatic
neuroendocrine tumors (GEP-NET) is a minute unobtrusive primary
tumor which often cannot be detected by common physical examinations. It therefore remains unidentified until the
tumor has spread and space-occupying
metastases cause clinical symptoms leading to diagnosis. Cases in which the primary cannot be located are referred to as NET with CUP-syndrome (
cancer of unknown primary syndrome). With the help of array-CGH (comparative genomic hybridization, Agilent 105K) and gene expression analysis (Agilent 44K), microdissected primaries and their
metastases were compared to identify up- and down-regulated genes which can be used as a marker for
tumor progression. In a next analysis step, a hierarchical clustering of 41.078 genes revealed three genes [
C-type lectin domain family 13 member A (CD302),
peptidylprolyl isomerase containing WD40 repeat (PPWD1) and abhydrolase domain containing 14B (ABHD14B)] which expression levels can categorize the
metastases into three groups depending on the localization of their primary. Because
cancer therapy is dependent on the localization of the primary, the gene expression level of these three genes are promising markers to unravel the CUP syndrome in NET.