title: IGF-1 receptor and IGF binding protein-3 might predict prognosis of patients with resectable pancreatic cancer.
abstract: BACKGROUND
  The present study aimed to elucidate the clinicopathologic role of insulin-like growth factor-1 receptor (IGF1R) and IGF binding protein-3 (IGFBP3) in patients with pancreatic cancer. The function of IGFBP3 is controversial, because both inhibition and facilitation of the action of IGF as well as IGF-independent effects have been reported. In this study, IGF1R and IGFBP3 expression was examined, and their potential roles as prognostic markers in patients with pancreatic cancer were evaluated.
  
  
  METHODS
  Clinicopathological features of 122 patients with curatively resected pancreatic cancer were retrospectively reviewed, and expression of IGF1R and IGFBP3 was immunohistochemically analyzed.
  
  
  RESULTS
  Expression of IGF1R and IGFBP3 was observed in 50 (41.0%) and 37 (30.3%) patients, respectively. IGF1R expression was significantly associated with histological grade (p = 0.037). IGFBP3 expression had a significant association with tumor location (p = 0.023), and a significant inverse association with venous invasion (p = 0.037). Tumors with IGF1R-positive and IGFBP3-negative expression (n = 32) were significantly frequently Stage II and III (p = 0.011). The prognosis for IGF1R positive patients was significantly poorer than that for IGF1R negative patients (p = 0.0181). IGFBP3 protein expression did not correlate significantly with patient survival. The subset of patients with both positive IGF1R and negative IGFBP3 had worse overall survival (8.8 months versus 12.6 months, respectively, p < 0.001).
  
  
  CONCLUSIONS
  IGF1R signaling might be associated with tumor aggressiveness, and IGFBP3 might show antiproliferative effects in pancreatic cancer. Both high IGF1R expression and low IGFBP3 expression represent useful prognostic markers for patients with curatively resected pancreatic cancer.
authors: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Osaka, Abeno-ku, Japan.
authors: Toshiki
authors: T
authors: Hirakawa
authors: Masakazu
authors: M
authors: Yashiro
authors: Akihiro
authors: A
authors: Murata
authors: Keiichiro
authors: K
authors: Hirata
authors: Kenjiro
authors: K
authors: Kimura
authors: Ryosuke
authors: R
authors: Amano
authors: Nobuya
authors: N
authors: Yamada
authors: Bunzo
authors: B
authors: Nakata
authors: Kosei
authors: K
authors: Hirakawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D017526:Receptor, IGF Type 1
references: Int J Cancer. 2009 Mar 1;124(5):1045-53
references: 19058181
references: Acta Paediatr Suppl. 1999 Feb;88(428):37-45
references: 10102050
references: Semin Surg Oncol. 2003;21(1):19-22
references: 12923912
references: J Biol Chem. 1993 Jul 15;268(20):14964-71
references: 7686909
references: J Cell Physiol. 1994 Jan;158(1):69-78
references: 7505280
references: Mol Pathol. 2001 Jun;54(3):145-8
references: 11376125
references: Br J Rheumatol. 1996 Jun;35(6):515-22
references: 8670570
references: Cell. 1993 Oct 8;75(1):59-72
references: 8402901
references: CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300
references: 20610543
references: J Cell Physiol. 2003 Feb;194(2):108-16
references: 12494449
references: Endocrinology. 2002 Jul;143(7):2693-9
references: 12072403
references: Int J Biochem Cell Biol. 1996 Jun;28(6):619-37
references: 8673727
references: Endocr Rev. 2007 Feb;28(1):20-47
references: 16931767
references: Am J Physiol Endocrinol Metab. 2000 Jun;278(6):E967-76
references: 10826997
references: Cell. 1993 Oct 8;75(1):73-82
references: 8402902
references: Teratog Carcinog Mutagen. 2001;21(1):27-44
references: 11135319
references: Biochim Biophys Acta. 1997 Jun 7;1332(3):F105-26
references: 9196021
references: Br J Cancer. 1992 Mar;65(3):341-6
references: 1558785
references: Eur J Cancer. 2000 Jun;36(10):1224-8
references: 10882860
references: Pancreas. 2004 Apr;28(3):231-4
references: 15084962
references: Endocrinology. 1996 Jun;137(6):2286-92
references: 8641177
references: Ann Surg Oncol. 2012 Aug;19(8):2733-43
references: 22207048
references: J Am Coll Surg. 2004 May;198(5):722-31
references: 15110805
references: Endocr Rev. 2002 Dec;23(6):824-54
references: 12466191
references: Cancer Res. 1991 Apr 1;51(7):1898-903
references: 2004373
references: Cancer Res. 1995 May 15;55(10):2007-11
references: 7743492
references: Lancet. 2004 Apr 24;363(9418):1346-53
references: 15110491
references: Regul Pept. 1996 Mar 22;61(3):189-95
references: 8701035
references: J Gastrointest Surg. 2000 Nov-Dec;4(6):567-79
references: 11307091
references: Nat Rev Cancer. 2004 Jul;4(7):505-18
references: 15229476
references: Lancet Oncol. 2002 May;3(5):298-302
references: 12067807
references: Am J Pathol. 2007 Jun;170(6):1964-74
references: 17525264
references: Am J Physiol. 1995 Jun;268(6 Pt 1):E1057-64
references: 7541943
references: Endocr Rev. 1995 Apr;16(2):143-63
references: 7540132