[668] Gastrin-Releasing Peptide Receptor Pathway Immunoexpression Profile in Pancreatic Endocrine Tumors.

Thomas McDonald, Joshua M Lloyd, Douglas Hartman, Alyssa M Krasinskas, Raja R Seethala. UPMC, Pittsburgh, PA

Background: GRPR is known to be constitutively expressed in pancreatic islet cells, though its role in pancreatic endocrine tumors (PET) has not been studied. We herein evaluate a series of PET by immunohistochemistry (IHC) for GRPR, its downstream target pSTAT3, and also assess potential crosstalk with EGFR via TGF-a transactivation.
Design: A tissue microarray was constructed from 45 paraffin embedded tumors from 40 patient (cored in triplicate). Sections were then immunostained for GRPR, EGFR, pSTAT3, and TGF-a, as well as previously reported prognostic markers, CK19, and Ki-67. Ki-67 was scored as a percentage, while other markers were assigned an H-score (Product of staining intensity [0-3] and percentage. Range: 0-300). Results were correlated with various clinicopathologic parameters. For subgroup comparison, Ki-67 was dichotomized to <2% and ≥2%, while other markers were dichotomized based on 50th percentile of staining distribution.
Results: Table 1 summarizes correlations (Kaplan Meier method, log rank comparison). A Ki-67 ≥ 2% correlated with worse PFS and OS. While GRPR, pSTAT3, and TGF-a were frequently expressed in PET, there were no significant correlations with outcomes. Tumors with low GRPR did have a slight tendency to behave more aggressively. EGFR staining was not noted in any of the tumors. CK19 also showed no correlation with outcome.

  N5-year PFS (%)p value5-year OS (%)p value
Tumor Extentlimited to pancreas23870.049950.043
 peripancreatic invasion650 67 
Necrosisno81000.0081000.04
 yes10 0 
Metastaticno2696<0.001960.038
 yes6* 67 
T stage1161000.018  
 21070   
 3650   
GRPR<#9780.080890.229
 ≥#13100 100 
pSTAT3<#12740.176910.913
 ≥#1593 93 
TGF-a<#13850.984920.949
 ≥#1384 92 
CK19<#10900.5901000.297
 ≥#1681 88 
Ki67<2%22950.0061000.006
 ≥2%650 67 
# = 50th percentile; *all cases censored at 48 months, 17% surviving


Conclusions: GRPR is expressed and retained in the majority of PET, underscoring its potential role as a novel therapeutic target in PET. Decreased GRPR expression trends toward a more aggressive phenotype. However, other tested pathway components do not seem to have any prognostic value. Unlike Ki-67, CK19 has no prognostic value in this cohort.
Category: Gastrointestinal

Tuesday, March 1, 2011 1:00 PM

Poster Session IV # 68, Tuesday Afternoon

 

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