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K-ras mutation status correlates with the expression of VEGFR1, VEGFR2, and PDGFRα in colorectal cancer

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Aim

We initiated this study in order to analyze whether the expression level of targeted receptor tyrosine kinases (RTK) is associated with the K-ras mutation status.

Methods

The expression pattern of VEGFR1, VEGFR2, VEGFR3, PDGFRα, PDGFRβ, and EGFR1 was analyzed in 93 samples of human colorectal carcinoma samples and correlated with the K-ras mutation status as identified by PCR-RFLP.

Results

VEGFR1, VEGFR2, VEGFR3, PDGFRα, PDGFRβ, and EGFR1 were expressed at relevant levels in 95%, 46%, 46%, 85%, 62%, and 82%, respectively. K-ras mutations were present in 53% (codon 12, 47%; codon 13, 6%). Expression of VEGFR1 (P = 0.0263), VEGFR2 (P = 0.0466), and PDGFRα (P = 0.0063) was significantly linked to K-ras codon 12 or 13 mutation. In addition, co-expression of VEGFR2 and PDGFRα was significantly associated with K-ras mutation (P = 0.0145).

Conclusion

Our data reveal that specific RTKs are over-expressed in K-ras mutated cancers. It needs to be addressed in prospective studies whether these patients will benefit from tyrosine kinase inhibitors more than K-ras wild-type.

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References

  1. Greenlee RT, Murray T, Bolden S, Wingo PA (2000) Cancer statistics, 2000. CA Cancer J Clin 50:7–33

    Article  CAS  PubMed  Google Scholar 

  2. Weir HK, Thun MJ, Hankey BF et al (2003) Annual report to the nation on the status of cancer, 1975–2000, featuring the uses of surveillance data for cancer prevention and control. J Natl Cancer Inst 95:1276–1299

    PubMed  Google Scholar 

  3. August DA, Ottow RT, Sugarbaker PH (1984) Clinical perspective of human colorectal cancer metastasis. Cancer Metastasis Rev 3:303–324

    Article  CAS  PubMed  Google Scholar 

  4. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767

    Article  CAS  PubMed  Google Scholar 

  5. Cho KR, Vogelstein B (1992) Suppressor gene alterations in the colorectal adenoma–carcinoma sequence. J Cell Biochem Suppl 16G:137–141

    Article  CAS  PubMed  Google Scholar 

  6. Vogelstein B, Kinzler KW (1993) The multistep nature of cancer. Trends Genet 9:138–141

    Article  CAS  PubMed  Google Scholar 

  7. Smith G, Carey FA, Beattie J et al (2002) Mutations in APC, Kirsten-ras, and p53-alternative genetic pathways to colorectal cancer. Proc Natl Acad Sci U S A 99:9433–9438

    Article  CAS  PubMed  Google Scholar 

  8. Li E, Hristova K (2006) Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies. Biochemistry 45:6241–6251

    Article  CAS  PubMed  Google Scholar 

  9. Mobius C, Stein HJ, Becker I et al (2003) The “angiogenic switch” in the progression from Barrett's metaplasia to esophageal adenocarcinoma. Eur J Surg Oncol 29:890–894

    Article  CAS  PubMed  Google Scholar 

  10. Liu XE, Sun XD, Wu JM (2004) Expression and significance of VEGF-C and FLT-4 in gastric cancer. World J Gastroenterol 10:352–355

    CAS  PubMed  Google Scholar 

  11. Yonemura Y, Endo Y, Tabata K et al (2005) Role of VEGF-C and VEGF-D in lymphangiogenesis in gastric cancer. Int J Clin Oncol 10:318–327

    Article  CAS  PubMed  Google Scholar 

  12. Takahashi Y, Cleary KR, Mai M, Kitadai Y, Bucana CD, Ellis LM (1996) Significance of vessel count and vascular endothelial growth factor and its receptor (KDR) in intestinal-type gastric cancer. Clin Cancer Res 2:1679–1684

    CAS  PubMed  Google Scholar 

  13. Tokunaga A, Onda M, Okuda T et al (1995) Clinical significance of epidermal growth factor (EGF), EGF receptor, and c-erbB-2 in human gastric cancer. Cancer 75:1418–1425

    Article  CAS  PubMed  Google Scholar 

  14. Wang KL, Wu TT, Choi IS et al (2007) Expression of epidermal growth factor receptor in esophageal and esophagogastric junction adenocarcinomas: association with poor outcome. Cancer 109:658–667

    Article  CAS  PubMed  Google Scholar 

  15. Drescher D, Moehler M, Gockel I et al (2007) Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma—a rationale for a molecular targeting strategy? World J Gastroenterol 13:3605–3609

    CAS  PubMed  Google Scholar 

  16. Schimanski CC, Linnemann U, Berger MR (1999) Sensitive detection of K-ras mutations augments diagnosis of colorectal cancer metastases in the liver. Cancer Res 59:5169–5175

    CAS  PubMed  Google Scholar 

  17. Argraves WS, Drake CJ (2005) Genes critical to vasculogenesis as defined by systematic analysis of vascular defects in knockout mice. Anat Rec A Discov Mol Cell Evol Biol 286:875–884

    PubMed  Google Scholar 

  18. Stadler WM (2005) Targeted agents for the treatment of advanced renal cell carcinoma. Cancer 104:2323–2333

    Article  CAS  PubMed  Google Scholar 

  19. An P, Lei H, Zhang J et al (2004) Suppression of tumor growth and metastasis by a VEGFR-1 antagonizing peptide identified from a phage display library. Int J Cancer 111:165–173

    Article  CAS  PubMed  Google Scholar 

  20. Hanrahan V, Currie MJ, Gunningham SP et al (2003) The angiogenic switch for vascular endothelial growth factor (VEGF)-A, VEGF-B, VEGF-C, and VEGF-D in the adenoma–carcinoma sequence during colorectal cancer progression. J Pathol 200:183–194

    Article  CAS  PubMed  Google Scholar 

  21. Simiantonaki N, Taxeidis M, Jayasinghe C, Kirkpatrick CJ (2007) Epithelial expression of VEGF receptors in colorectal carcinomas and their relationship to metastatic status. Anticancer Res 27:3245–3250

    PubMed  Google Scholar 

  22. Witte D, Thomas A, Ali N, Carlson N, Younes M (2002) Expression of the vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligand VEGF-C in human colorectal adenocarcinoma. Anticancer Res 22:1463–1466

    CAS  PubMed  Google Scholar 

  23. Wehler TC, Frerichs K, Graf C et al (2008) PDGFRalpha/beta expression correlates with the metastatic behavior of human colorectal cancer: a possible rationale for a molecular targeting strategy. Oncol Rep 19:697–704

    CAS  PubMed  Google Scholar 

  24. Spano JP, Lagorce C, Atlan D et al (2005) Impact of EGFR expression on colorectal cancer patient prognosis and survival. Ann Oncol 16:102–108

    Article  PubMed  Google Scholar 

  25. Gamboa-Dominguez A, Dominguez-Fonseca C, Quintanilla-Martinez L et al (2004) Epidermal growth factor receptor expression correlates with poor survival in gastric adenocarcinoma from Mexican patients: a multivariate analysis using a standardized immunohistochemical detection system. Mod Pathol 17:579–587

    Article  CAS  PubMed  Google Scholar 

  26. Kopp R, Rothbauer E, Ruge M et al (2003) Clinical implications of the EGF receptor/ligand system for tumor progression and survival in gastrointestinal carcinomas: evidence for new therapeutic options. Recent Results Cancer Res 162:115–132

    CAS  PubMed  Google Scholar 

  27. Linnemann U, Schimanski CC, Gebhardt C, Berger MR (2004) Prognostic value of disseminated colorectal tumor cells in the liver: results of follow-up examinations. Int J Colorectal Dis 19:380–386

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. First Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, Mainz, 55101, Germany

    Carl C. Schimanski, Tim Zimmermann, Peter R. Galle & Markus Moehler

  2. Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), Johannes Gutenberg University of Mainz, Mainz, Germany

    Irene Schmidtmann

  3. Department of General and Abdominal Surgery, Johannes Gutenberg University of Mainz, Mainz, Germany

    Ines Gockel & Hauke Lang

  4. Unit of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg, Germany

    Martin R. Berger

Authors
  1. Carl C. Schimanski
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  2. Tim Zimmermann
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  3. Irene Schmidtmann
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  4. Ines Gockel
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  5. Hauke Lang
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  6. Peter R. Galle
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  7. Markus Moehler
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  8. Martin R. Berger
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Correspondence to Carl C. Schimanski.

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Schimanski, C.C., Zimmermann, T., Schmidtmann, I. et al. K-ras mutation status correlates with the expression of VEGFR1, VEGFR2, and PDGFRα in colorectal cancer. Int J Colorectal Dis 25, 181–186 (2010). https://doi.org/10.1007/s00384-009-0843-7

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  • DOI: https://doi.org/10.1007/s00384-009-0843-7

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