Overexpression of Membrane Proteins in Primary and Metastatic Gastrointestinal Neuroendocrine Tumors

• Published in: Annals of surgical oncology 2013-12, Vol.20 (Suppl 3), p.739-746
• Main Authors: Carr, Jennifer C., Sherman, Scott K., Wang, Donghong, Dahdaleh, Fadi S., Bellizzi, Andrew M., O’Dorisio, M. Sue, O’Dorisio, Thomas M., Howe, James R.
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Gastrointestinal Neoplasms - genetics; Gastrointestinal Neoplasms - metabolism; Gastrointestinal Neoplasms - pathology; Humans; Immunoenzyme Techniques; Intestine, Small - metabolism; Intestine, Small - pathology; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - secondary; Lymphatic Metastasis; Medicine; Medicine & Public Health; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metalloendopeptidases - genetics; Metalloendopeptidases - metabolism; Mucins - genetics; Mucins - metabolism; Neoplasm Staging; Neuroendocrine Tumors - genetics; Neuroendocrine Tumors - metabolism; Neuroendocrine Tumors - pathology; Oncology; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Prognosis; Real-Time Polymerase Chain Reaction; Receptors, Oxytocin - genetics; Receptors, Oxytocin - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Surgery; Surgical Oncology; Translational Research and Biomarkers
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-013-3318-6

Background Small bowel and pancreatic neuroendocrine tumors (SBNETs and PNETs) are rare tumors whose incidence is increasing. Drugs targeting the somatostatin receptor are beneficial in these tumors. To identify additional cell-surface targets, we recently found receptors and membrane proteins with gene expression significantly different from adjacent normal tissues in a small number of primary SBNETs and PNETs. We set out to validate these expression differences in a large group of primary neuroendocrine tumors and to determine whether they are present in corresponding liver and lymph node metastases. Methods Primary SBNETs and PNETs, normal tissue, nodal, and liver metastases were collected and mRNA expression of six target genes was determined by quantitative PCR. Expression was normalized to GAPDH and POLR2A internal controls, and differences as compared to normal tissue were assessed by Welch’s t test. Results Gene expression was determined in 45 primary PNETs with 20 nodal and 17 liver metastases, and 51 SBNETs with 50 nodal and 29 liver metastases. Compared to normal tissue, the oxytocin receptor ( OXTR ) showed significant overexpression in both primary and metastatic SBNETs and PNETs. Significant overexpression was observed for MUC13 and MEP1B in PNET primary tumors, and for GPR113 in primary SBNETs and their metastases. SCTR and ADORA1 were significantly underexpressed in PNETs and their metastases. OXTR protein expression was confirmed by immunohistochemistry. Conclusions OXTR is significantly overexpressed relative to normal tissue in primary SBNETs and PNETs, and this overexpression is present in their liver and lymph node metastases, making OXTR a promising target for imaging and therapeutic interventions.