Biomarker Expression in Pancreatic Endocrine Tumors.
Laura J Adhikari, Judith A Gilbert, Ricardo V Lloyd, Matthew M Ames. Mayo Clinic, Rochester, MN; University of Wisconsin School of Medicine, Madison
Background: Pancreatic endocrine tumors (PET) represent 1-2% of all pancreatic neoplasms. Complete surgical resection is the most successful treatment for patients with PETs; however, some patients present with advanced disease for which few treatment options exist. Somatostatin therapy can ameliorate clinical symptoms and perhaps induce tumor growth stabilization, but PETs have poor or short-lived rates of response to conventional chemotherapeutic agents [Gastroenterology 2008, 135:1469] and novel therapeutic strategies are needed.
Design: We assessed 67 PETs from 44 patients for immunohistochemical expression of biomarkers targeted by novel therapeutic drugs currently under development in other forms of cancer. A tissue microarray of 67 formalin-fixed, paraffin-embedded tissues with each tissue represented as a triplicate of 0.6mm cores were evaluated. Primary neoplasms from 41 of these patients were included in the data. The markers include insulin-like growth factor 1 receptor (IGF1R), transforming growth factor-ß receptor 1 (TGFBR1), heat shock protein 90 (Hsp90), somatostatin receptor subtypes 2A and 5 (SSTR2A and SSTR5), platelet-derived growth factor alpha (PDGFA), O6-methylguanine DNA methyltransferase (MGMT), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 1 (VEGFR1), and mammalian target of rapamycin (mTOR).
Results: All of the assessable PETs stained positively for IGF1R, TGFBR1, Hsp90, SSTR5, SSTR2A, and PDGFRA, with 98% positivity with EGFR, VEGFR1, and mTOR. 24% of the PETs were negative for MGMT (predictive of a favorable response to temozolomide therapy [Clin Cancer Res 2009:15:338]), and 52% were weakly staining for MGMT. Proteins for which the largest number of PETs exhibited the strongest staining level (score of 3) were VEGFR1 (80% of PETS), and TGFBR1 (69%), PDGFRA (65%), SSTR2A (55%), SSTR5 (55%), and IGF1R (47%).
Conclusions: High immunohistochemical expression of VEGFR1, TGFBR1, PDGFRA, and IGFR1 is encouraging of additional research into the role played by these proteins in PET growth. Lack of MGMT immunohistochemical expression in some PETs suggests that temozolomide might be a useful therapeutic agent.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 53, Tuesday Afternoon