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.
|N||5-year PFS (%)||p value||5-year OS (%)||p value|
|Tumor Extent||limited to pancreas||23||87||0.049||95||0.043|