Metastasis Suppressors KISS-1, RKIP and GPR54 Are Expressed in Pancreatic Neuroendocrine Tumors and Their Expression Is Altered in Metastases
Benjamin J Swanson, Lawrence A Shirley, Mark Bloomston, Wendy L Frankel. Ohio State University Wexner Medical Center, Columbus, OH
Background: Pancreatic neuroendocrine tumors (PNET) are a group of neoplasms whose metastatic potential and lethality can be difficult to predict. Metastasis suppressors have biologic effects on metastasis but do not impact tumorigenicity. Kisspeptin-1 (KISS-1) and Raf kinase inhibitory protein (RKIP) are metastasis suppressors known to play biological roles in pancreatic islet cells. GPR54 is a putative receptor for KISS1. These proteins have not been studied in PNET, thus we sought to determine their expression and biological impact in PNET.
Design: Tissue microarrays (TMAs) of PNET (n=107) were constructed from archived samples. These TMAs consisted of both primary (n=85) as well as paired and unpaired metastatic samples (n=22). TMAs were immunohistochemically stained for KISS-1, RKIP and GPR54 and scored as strongly positive (2+), weakly positive (1+), or negative (0).
Results: The expression of KISS-1, RKIP and GPR54 are shown in Table 1.
|KISS-1||Primary||15% (13/85)||38% (32/85)||47% (40/85)|
|KISS-1||Metastasis||5% (1/22)||59% (13/22)||36% (8/22)|
|RKIP||Primary||46% (38/82)*||44% (36/82)||10% (8/82)|
|RKIP||Metastasis||33% (7/21)*||38% (8/21)||29% (6/21)|
|GPR54||Primary||24% (20/82)||42% (34/82)||34% (28/82)|
|GPR54||Metastasis||14% (3/21)||38% (8/21)||47% (10/21)|
|Presence of Metastasis||0.033**||0.184||0.727|
|Length of Survival||0.320||0.136||0.936|