An Analysis of Trends and Growth Factor Receptor Expression of GI Carcinoid Tumors

Abstract

The purpose of our study was twofold: 1) to determine the incidence, patient and tumor characteristics, and outcome of patients with GI carcinoid tumors using the Surveillance, Epidemiology and End Results (SEER) database, and 2) to delineate the expression pattern of growth factor receptors (GFRs) in carcinoid tumors. The SEER database search provided information on patients diagnosed with carcinoid tumors from 1990-2002. Carcinoid tumor sections (n = 46) were stained for the GFRs: epidermal growth factor receptor (EGFR), insulin-like growth factor receptor (IGFR), vascular endothelial growth factor receptor (VEGFR), and HER-2/neu. Over the 12 year analysis period, 18,180 patients were identified with carcinoid tumors of the foregut, midgut, and hindgut; the incidence of carcinoid tumors increased ~2-fold during this time period. Of the patients with carcinoid tumors, there was a trend of increased expression of VEGF-R and IGF-R, particularly in the foregut and midgut carcinoids. Analysis of the SEER database confirms that the incidence of carcinoid tumors is increasing with an approximate doubling in the number of carcinoid cases from 1990-2002. Furthermore, an increase in VEGF-R and IGF-R expression suggests that GFR inhibitors may be effective adjuvant therapy for carcinoid cancer.

VEGFR‐2 expression in carcinoid cancer cells and its role in tumor growth and metastasis

“…32 Previously, we detected the presence of VEGFR-2 in the epithelial component of ∼48% (22 of 46) of carcinoid tumors. 11 As VEGFR-2 expression is generally confined to endothelial cells surrounding blood vessels, 9,10 the finding of VEGFR-2 in carcinoid tumors prompted us to assess the expression of VEGFR-2 in the BON carcinoid cell line. BON cells express VEGFR-2, as indicated by Western blot analysis and immunocytochemistry (Figs.…”

“…9,10 Previously, we detected the presence of VEGFR-2 in ∼48% of carcinoid tumors with the highest expression in foregut and hindgut carcinoids. 11 VEGFR-2, also designated as kinase domain receptor (KDR), is a tyrosine kinase that can signal through the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) pathway. 9,10 When VEGF binds to its receptor, it activates the PI3K protein, which is made up of a p85 regulatory subunit and a p110 catalytic subunit.…”

Phase I study of sorafenib in combination with everolimus (RAD001) in patients with advanced neuroendocrine tumors

“…Additionally, preclinical studies have demonstrated that neuroendocrine tumors have increased expression of VEGF, VEGF receptor-2 (VEGFR-2), and other growth factor receptors including platelet-derived growth factor receptors (PDGFRs) α and β, and stem-cell factor receptor (c-kit) [4–8]. A recent randomized, placebo-controlled trial demonstrated improved progression-free survival of patients with advanced pancreatic NET treated with the tyrosine kinase inhibitor sunitinib [9].…”

New Pharmacologic Therapies for Gastroenteropancreatic Neuroendocrine Tumors

“…In contrast to many adenocarcinomas, they seldom express microsatellite instability and mutations in the Ras-Raf-MAPKinase or the TGFβ pathway (22, 23). Molecular profiling of tumors instead shows over-expression of the phosphoinotiside-3 kinase - Akt - mammalian target of rapamycin (PI3K-Akt-mTOR) pathway, and the insulin-like growth factor-1 receptor (24, 25, 26). Administering a pharmacologic agent that inhibits one or more of these pro-proliferative proteins provides a rationale for patient- or tumor-specific therapy, and has been tested in early-stage clinical trials.…”