title: Chromogranin A, Ki-67 index and IGF-related genes in patients with neuroendocrine tumors.
abstract: Chromogranin A (CgA) and the Ki-67 proliferation index are considered as important biochemical and pathological markers for clinical behaviour of gastroenteropancreatic neuroendocrine tumors (GEP NETs), respectively. The IGF system has been suggested as an important regulator of GEP NET proliferation and differentiation. A possible relationship between serum CgA (sCgA), Ki-67 proliferation index, and expression of IGF-related genes in patients with GEP NETs has not been demonstrated yet. This study investigates the relationship between sCgA, the Ki-67 proliferation index, and the expression of IGF-related genes in GEP NET tissues and their relation with 5-year survival. Tumor and blood samples from 22 GEP NET patients were studied.
  IGF1, IGF2; IGF receptors: IGF1R, IGF2R; insulin receptors: subtype A (IR-A) and B (IR-B); IGF-binding proteins (IGFBPs): IGFBP1, IGFBP2, IGFBP3, and IGFBP6) was measured using quantitative RT-PCR. Ki-67 proliferation index was determined using immunohistochemistry. sCgA was measured with ELISA. Five-year survival in patients with nonelevated sCgA (n=11) was 91 vs 46% in patients with elevated sCgA (n=11) (P=0.006). IR-A mRNA expression was significantly higher in tumors obtained from patients with elevated sCgA than in those from patients with nonelevated sCgA (6.42±2.08 vs 2.60±0.40; P=0.04). This data suggests that sCgA correlates well with 5-year survival of GEP NET patients, and that IR-A mRNA expression correlates well with tumor mass in GEP NET patients.
authors.affiliation: Department of Internal MedicineSector of Endocrinology, Erasmus MC, 's Gravendijkwal 230, Room D-430, 3015 CE Rotterdam, The Netherlands Department of SurgeryErasmus MC, Rotterdam, The Netherlands Department of PathologyErasmus MC, Rotterdam, and Reinier de Graaf Hospital, Delft, The Netherlands.
authors.forename: R C S
authors.initials: RC
authors.lastname: van Adrichem
authors.forename: L J
authors.initials: LJ
authors.lastname: Hofland
authors.forename: R A
authors.initials: RA
authors.lastname: Feelders
authors.forename: M C
authors.initials: MC
authors.lastname: De Martino
authors.forename: P M
authors.initials: PM
authors.lastname: van Koetsveld
authors.forename: C H J
authors.initials: CH
authors.lastname: van Eijck
authors.forename: R R
authors.initials: RR
authors.lastname: de Krijger
authors.forename: D M
authors.initials: DM
authors.lastname: Sprij-Mooij
authors.forename: J A M J L
authors.initials: JA
authors.lastname: Janssen
authors.forename: W W
authors.initials: WW
authors.lastname: de Herder
keywords: IGF-related genes; Ki-67 proliferation index; gastroenteropancreatic neuroendocrine tumors (GEP NETs); serum chromogranin A (sCgA)
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