[1798] 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.

Table 1. Expression of KISS-1, RKIP, and GPR54 in Primary and Metastatic PNET
  Score
ProteinSite2+1+0
KISS-1Primary15% (13/85)38% (32/85)47% (40/85)
KISS-1Metastasis5% (1/22)59% (13/22)36% (8/22)
RKIPPrimary46% (38/82)*44% (36/82)10% (8/82)
RKIPMetastasis33% (7/21)*38% (8/21)29% (6/21)
GPR54Primary24% (20/82)42% (34/82)34% (28/82)
GPR54Metastasis14% (3/21)38% (8/21)47% (10/21)
*-Statistically Significant

RKIP was statistically down-regulated (p= 0.027) in metastatic tumors compared to primary tumors, while there were no significant differences in KISS-1 and GPR54. Furthermore, the expression of KISS-1 strongly correlated with the expression of GPR-54 (p<0.001). Correlation between expression levels of KISS-1, RKIP, GPR54 with tumor and clinical parameters are presented in Table 2.

Table 2. Correlation between KISS-1, RKIP and GPR54 and Pathological and Clinical Parameters
 KISS-1RKIPGPR54
 ppp
Mitotic Count0.9350.090.951
Ki-670.7850.026**0.982
Tumor Size0.1240.3740.983
Presence of Metastasis0.033**0.1840.727
Length of Survival0.3200.1360.936
**-Statistically Significant

Overexpression of KISS-1 was associated with the presence of metastasis while absence of RKIP expression was associated with a higher Ki-67 proliferation rate.
Conclusions: These results suggest that KISS-1, RKIP and GPR54 are expressed in PNET and that RKIP may act as a metastasis suppressor due to its loss in metastatic lesions. Finally, overexpression of KISS-1 may promote metastasis.
Category: Pancreas

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 274, Monday Morning

 

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