Digestive Diseases and Sciences

, Volume 52, Issue 1, pp 248–253 | Cite as

Expression of IGFBP2 in Gastric Carcinoma and Relationship With Clinicopathologic Parameters and Cell Proliferation

  • Lihua Zhang
  • Wenbin Huang
  • Jieyu Chen
  • Xiaojun ZhouEmail author
  • Zhenfeng Lu
  • Hangbo Zhou
Original Paper


The insulin-like growth factor (IGF) axis is a complex system composed of two mitogenic ligands, IGF-I and IGF-II, two receptors, IGF-IR and IGF-IIR, and six binding proteins, IGFBP1 to IGFBP6. The IGFBPs exert their actions through their regulation of IGF bioavailability for IGF receptors. The present study evaluated the correlation between IGFBP2 expression and clinicopathologic parameters and cell proloferation in cancer by using surgically resected tissue specimens from 97 patients with gastric carcinoma treated at our hospital. Immunohistochemical staining was performed using IGFBP2 and Ki-67 monoclonal antibody. An obvious difference existed in the IGFBP2 expression between carcinomas and normal mucosa. Correlation between IGFBP2 expression and the depth of penetration, lymph node metastasis, and clinical stage were observed. There was positive correlation between IGFBP2 expression and Ki-67 expression. We conclude that IGFBP2 may be involved in carcinogenesis and progression of gastric carcinoma by promoting cell proliferation.


Insulin-like growth factor binding protein Gastric carcinoma Ki-67 Cell proliferation 


  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P (2000) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94:153–156CrossRefGoogle Scholar
  2. 2.
    Konturek PC, Konturek SJ, Sulekova Z, Meixner H, Bielanski W, Starzynska T, Karczewska E, Marlicz K, Stachura J, Hahn EG (2001) Expression of hepatocyte growth factor, transforming growth factor alpha, apoptosis related proteins Bax and Bcl-2, and gastrin in human gastric cancer. Aliment Pharmacol Ther 15:989–999PubMedCrossRefGoogle Scholar
  3. 3.
    Han SU, Lee JH, Kim WH, Cho YK, Kim MW (1999) Significant correlation between serum level of hepatocyte growth factor and progression of gastric carcinoma. World J Surg 23:1176–1180PubMedCrossRefGoogle Scholar
  4. 4.
    Rosenfeld RG, Roberts CT (eds) (1999) The IGF System. Totowa, NJ: Humana Press Inc.Google Scholar
  5. 5.
    LeRoith D (1996) Insulin-like growth factor receptors and binding proteins. Baillieres Clin Endocrinol Metab 10:49–73PubMedCrossRefGoogle Scholar
  6. 6.
    Rajaram S, Baylink DJ, Mohan S (1997) Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions. Endocr Rev 18:801–831PubMedCrossRefGoogle Scholar
  7. 7.
    Wetterau LA, Moore MG, Lee KW, Shim ML, Cohen P (1999) Novel aspects of the insulin-like growth factor binding proteins. Molecular Genetics Metab 68:161–181CrossRefGoogle Scholar
  8. 8.
    Hoeflich A, Lahm H, Blum W, Kolb H, Wolf E (1998) Insulin-like growth factor-binding protein-2 inhibits proliferation of human embryonic kidney fibroblasts and of IGF-responsive colon carcinoma cell lines. FEBS Lett 434:329–334CrossRefGoogle Scholar
  9. 9.
    Hoeflich A, Nedbal S, Blum WF, Erhard M, Lahm H, Brem G, Kolb HJ, Wanke R, Wolf E (2001) Growth inhibition in giant growth hormone transgenic mice by overexpression of insulin-like growth factor-binding protein-2. Endocrinology 142:1889–1898PubMedCrossRefGoogle Scholar
  10. 10.
    Flyvbjerg A, Mogensen O, Mogensen B, Nielsen OS (1997) Elevated serum insulin-like growth factor-binding protein 2 (IGFBP-2) and decreased IGFBP-3 in epithelial ovarian cancer: correlation with cancer antigen 125 and tumor-associated trypsin inhibitor. J Clin Endocrinol Metab 82:2308–2313PubMedCrossRefGoogle Scholar
  11. 11.
    El Atiq F, Garrouste F, Remacle-Bonnet M, Sastre B, Pommier G (1994) Alterations in serum levels of insulin-like growth factors and insulin-like growth-factor binding proteins in patients with colorectal cancer. Int J Cancer 57:491–497PubMedCrossRefGoogle Scholar
  12. 12.
    Ho PJ, Baxter RC (1997) Insulin-like growth factor-binding protein-2 in patients with prostate carcinoma and benign prostatic hyperplasia. Clin Endocrinol 46:333–342CrossRefGoogle Scholar
  13. 13.
    Muller HL, Oh Y, Lehrnbecher T, Blum WF, Rosenfeld RG (1994) Insulin-like growth factor-binding protein-2 concentrations in cerebrospinal fluid and serum of children with malignant solid tumors or acute leukemia. J Clin Endocrinol Metab 79:428–434PubMedCrossRefGoogle Scholar
  14. 14.
    Schutt BS, Langkamp M, Rauschnabel U, Ranke MB, Elmlinger MW (2004) Integrin-mediated action of insulin-like growth factor binding protein-2 in tumor cells. J Mol Endocrinol 32:859–868PubMedCrossRefGoogle Scholar
  15. 15.
    Moore MG, Wetterau LA, Francis MJ, Peehl DM, Cohen P (2003) Novel stimulatory role for insulin-like growth factor binding protein-2 in prostate cancer cells. Int J Cancer 105:14–19PubMedCrossRefGoogle Scholar
  16. 16.
    Yi HK, Hwang PH, Yang DH, Kang CW, Lee DY (2001) Expression of the insulin-like growth factors (IGFs) and the IGF-binding proteins(IGFBPs) in human gastric cancer cells. Eur J Cancer 37:2257PubMedCrossRefGoogle Scholar
  17. 17.
    He T, Wu XT, Yang ZM, Da MX, Zhang MM, Qian K (2005) IGFBP-2 mRNA expression in gastric cancer tissues and its roles in proliferation, differentiation and peritoneal metastasis of gastric cancer. SiChuan Da Xue Xue Bao Yi Xue Ban 36:187–189PubMedGoogle Scholar
  18. 18.
    Pinto-de-Sousa J, David L, Seixas M, Pimenta A (2001) Clinicopathologic profiles and prognosis of gastric carcinomas from the cardia, fundus/body and antrum. Dig Surg 18:102–110PubMedCrossRefGoogle Scholar
  19. 19.
    Sobin LE, Whitekind CH (eds) (2001) TNM classification of malignant tumours. International Union Against Cancer, 5th ed. New York: John Wiley & SonsGoogle Scholar
  20. 20.
    Cohen P, Peehl DM, Stamey TA, Wilson KF, Clemmons DR, Rosenfeld RG (1993) Elevated levels of insulin-like growth factor-binding protein-2 in the serum of prostate cancer patients. J Clin Endocrinol Metab 76:1031–1035PubMedCrossRefGoogle Scholar
  21. 21.
    Kanety H, Madjar Y, Dagan Y, Levi J, Papa MZ, Pariente C, Goldwasser B, Karasik A (1993) Serum insulin-like growth factor-binding protein-2 (IGFBP-2) is increased and IGFBP-3 is decreased in patients with prostate cancer: correlation with serum prostate-specific antigen. J Clin Endocrinol Metab 77:229–233PubMedCrossRefGoogle Scholar
  22. 22.
    Boulle N, Logie A, Gicquel C, Perin L, Le Bouc Y (1998) Increased levels of insulin-like growth factor II (IGF-II) and IGF-binding protein-2 are associated with malignancy in sporadic adrenocortical tumors. J Clin Endocrinol Metab 83:1713–1720PubMedCrossRefGoogle Scholar
  23. 23.
    Wex H, Vorwerk P, Mohnike K, Bretschneider D, Kluba U, Aumann V, Blum WF, Mittler U (1998) Elevated serum levels of IGFBP-2 found in children suffering from acute leukaemia is accompanied by the occurrence of IGFBP-2 mRNA in the tumour clone. Br J Cancer 78:515–520PubMedGoogle Scholar
  24. 24.
    Busund LT, Richardsen E, Busund R, Ukkonen T, Bjornsen T, Busch C, Stalsberg H (2005) Significant expression of IGFBP2 in breast cancer compared with benign lesions. J Clin Pathol 58:361–366PubMedCrossRefGoogle Scholar
  25. 25.
    Richardsen E, Ukkonen T, Bjnren T, Mortensen E, Egevad L, Busch C (2003) Overexpression of IGFBP2 is a marker for malignant transformation in prostate epithelium. Virchows Arch 442:329–335PubMedGoogle Scholar
  26. 26.
    Song SW, Fuller GN, Khan A, Kong S, Shen W, Taylor E, Ramdas L, Lanf FF, Zhang W (2003) IIp45, an insulin-like growth factor binding protein 2 (IGFBP2) binding protein, antagonizes IGFBP2 stimulation of glioma cell invasion. PNAS 100:13970–13975PubMedCrossRefGoogle Scholar
  27. 27.
    Bubendorf L, Kolmer M, Kononen J, Koivisto P, Mousses S, Chen Y, Mahlamaki E, Schraml P, Moch H, Willi N, Elkahloun AG, Pretlow TG, Gasser TC, Mihatsch MJ, Sauter G, Kallioniemi OP (1999) Hormone therapy failure in human prostate cancer: analysis by complementary DNA and tissue microarrays. J Natl Cancer Inst (Bethesda) 91:1758–1764CrossRefGoogle Scholar
  28. 28.
    Fuller GN, Rhee CH, Hess KR, Caskey LS, Wang R, Bruner JM, Yung WK, Zhang W (1999) Reactivation of insulin-like growth factor binding protein 2 expression in glioblastoma multiforme: a revelation by parallel gene expression profiling. Cancer Res 59:4228–4232PubMedGoogle Scholar
  29. 29.
    Sato T, Yoshinaga K, Okabe S, Okawa T, Higuchi T, Enomoto M, Takizawa T, Sugihara K (2003) Cyclooxygenase-2 expression and its relationship with proliferation of colorectal adenomas. Jpn J Clin Oncol 33:631–635PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Lihua Zhang
    • 1
  • Wenbin Huang
    • 1
  • Jieyu Chen
    • 1
  • Xiaojun Zhou
    • 1
    Email author
  • Zhenfeng Lu
    • 1
  • Hangbo Zhou
    • 1
  1. 1.Department of Pathology, Jinling HospitalClinical School of Medical College of Nanjing UniversityNanjingP.R. China

Personalised recommendations