[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 50^th 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.

		N	5-year PFS (%)	p value	5-year OS (%)	p value
Tumor Extent	limited to pancreas	23	87	0.049	95	0.043
	peripancreatic invasion	6	50		67
Necrosis	no	8	100	0.008	100	0.04
	yes	1	0		0
Metastatic	no	26	96	<0.001	96	0.038
	yes	6	*		67
T stage	1	16	100	0.018
	2	10	70
	3	6	50
GRPR	<#	9	78	0.080	89	0.229
	≥#	13	100		100
pSTAT3	<#	12	74	0.176	91	0.913
	≥#	15	93		93
TGF-a	<#	13	85	0.984	92	0.949
	≥#	13	84		92
CK19	<#	10	90	0.590	100	0.297
	≥#	16	81		88
Ki67	<2%	22	95	0.006	100	0.006
	≥2%	6	50		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