title: Epidermal growth factor receptor and activated epidermal growth factor receptor expression in gastrointestinal carcinoids and pancreatic endocrine carcinomas.
abstract: The epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of many tumors. To analyze the expression of EGFR and activated EGFR in well-differentiated neuroendocrine carcinomas including primary and metastatic gastrointestinal carcinoid tumors and pancreatic endocrine tumors (PET), we examined 58 gastrointestinal carcinoid tumors and 48 PET using immunohistochemistry, Western blotting, and RT-PCR. EGFR and activated EGFR (P-EGFR) were expressed by both gastrointestinal carcinoids and PET in primary and metastatic tumors, although a higher percentage of gastrointestinal carcinoid tumors expressed EGFR and activated EGFR. Western blotting detected a 170 kDa band for both EGFR and activated EGFR in three primary carcinoid tumors and two metastatic carcinoid tumors to the liver. RT-PCR analysis confirmed the expression of EGFR mRNA in both primary and metastatic carcinoid tumors. Patients with activated EGFR expression in their primary PET had a significantly worse prognosis compared to those who did not express activated-EGFR (P = 0.043). These results indicate that gastrointestinal carcinoid tumors as well as PET express EGFR and activated EGFR, and that expression is more common in gastrointestinal carcinoid tumors compared to pancreatic endocrine tumors. These findings implicate the EGFR and P-EGFR signal transduction pathway in the pathogenesis of these neuroendocrine tumors and suggest that targeted therapy directed against the EGFR tyrosine kinase domain may be a useful therapeutic approach in patients with unresectable metastatic gastrointestinal carcinoid tumors and pancreatic endocrine tumors.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Bettina
authors.initials: B
authors.lastname: Papouchado
authors.forename: Lori A
authors.initials: LA
authors.lastname: Erickson
authors.forename: Audrey L
authors.initials: AL
authors.lastname: Rohlinger
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Hobday
authors.forename: Charles
authors.initials: C
authors.lastname: Erlichman
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Ames
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: Lloyd
mesh_terms: D015153:Blotting, Western; D002276:Carcinoid Tumor / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000378:metabolism; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D066246:ErbB Receptors