Skip to main content

Advertisement

SpringerLink
Log in

Diffuse Expression of RNA-Binding Protein IMP3 Predicts High-Stage Lymph Node Metastasis and Poor Prognosis in Colorectal Adenocarcinoma

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

IMP3 (insulinlike growth factor II mRNA-binding protein 3) is a newly identified oncofetal RNA-binding protein that is involved in cell growth and cell migration during the early stages of embryogenesis. This study sought to elucidate its role in tumor progression and prognosis of colorectal adenocarcinoma (CRA).

Methods

IMP3 expression in 186 surgically resected unifocal primary CRAs was analyzed by immunohistochemistry. The proportions of tumor cells positive for IMP3 were scored into diffuse (≥50%), focal or heterogeneous (10–50%), and trace (<10%), and the expression levels were correlated with clinicopathologic features and patient survival.

Results

Cytoplasmic immunoreactivity for IMP3 was diffuse in 66 (35%), focal or heterogeneous in 38 (21%), and trace in 34 (18%) samples. No staining was seen in the adjacent nontumorous tissue. Diffuse IMP3 expression correlated with large tumor (>3 cm, P = .0452), high-stage tumor (IIIa–IV, P = .0417), lymph node metastasis (P = .0232), high lymph node ratio (LNR ≥ .7, P = .0016), and lower 5-year survival (P = .0012). Further analysis showed that patients with high-stage CRA and diffuse IMP3 expression had the worst survival rate (P < .0001)—far worse than those without diffuse IMP3 expression (P = .0038). Moreover, multivariant analysis showed diffuse IMP3 expression, serosal invasion, LNR, tumor stage, and adjuvant chemotherapy were independent prognostic factors in CRA.

Conclusion

Diffuse IMP3 protein expression correlates with invasion and aggressiveness during cancer growth and metastasis, and it is an important prognostic factor of CRAs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Zlobec I, Lugli A. Prognostic and predictive factors in colorectal cancer. J Clin Pathol. 2008;61:561–9.

    PubMed  CAS  Google Scholar 

  2. Liang JT, Cheng YM, Chang KJ, Chien CT, Hsu HC. Reappraisal of K-ras and p53 gene mutations in the recurrence of Dukes’ B2 rectal cancer after curative resection. Hepatogastroenterology. 1999;46:830–7.

    PubMed  CAS  Google Scholar 

  3. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82:4–6.

    Article  PubMed  CAS  Google Scholar 

  4. Eberhart CE, Coffey RJ, Radhika A, et al. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology. 1994;107:1183–8.

    PubMed  CAS  Google Scholar 

  5. Wang T, Fan L, Watanabe Y, et al. L523S, an RNAbinding protein as a potential therapeutic target for lung cancer. Br J Cancer. 2003;88:887–94.

    Article  PubMed  CAS  Google Scholar 

  6. Yantiss RK, Woda BA, Fanger GR, et al. KOC (Komology Domain Containing Protein Overexpressed in Cancer): a novel molecular marker that distinguishes between benign and malignant lesions of the pancreas. Am J Surg Pathol. 2005;29:188–95.

    Article  PubMed  Google Scholar 

  7. Nielsen J, Christiansen J, Lykke-Andersen J, et al. A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development. Mol Cell Biol. 1999;19:1262–70.

    PubMed  CAS  Google Scholar 

  8. Mueller-Pillasch F, Pohl B, Wilda M, et al. Expression of the highly conserved RNA binding protein KOC in embryogenesis. Mech Dev. 1999;88:95–9.

    Article  PubMed  CAS  Google Scholar 

  9. Li C, Rock KL, Woda BA, et al. IMP3 is a novel biomarker for adenocarcinoma in situ of the uterine cervix: an immunohistochemical study in comparison with p16(INK4a) expression. Mod Pathol. 2007;20:242–7.

    Article  PubMed  CAS  Google Scholar 

  10. Gress TM, Muller-Pillasch F, Geng M, et al. A pancreatic cancer-specific expression profile. Oncogene. 1996;13:1819–930.

    PubMed  CAS  Google Scholar 

  11. Wang T, Hopkins D, Schmidt C, et al. Identification of genes differentially over-expressed in lung squamous cell carcinoma using combination of cDNA subtraction and microarray analysis. Oncogene. 2000;19:1519–28.

    Article  PubMed  CAS  Google Scholar 

  12. Jiang Z, Chu P, Woda BA, et al. Analysis of RNA binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study. Lancet Oncol. 2006;7:556–64.

    Article  PubMed  CAS  Google Scholar 

  13. Hoffmann NE, Sheinin Y, Lohse CM, et al. External validation of IMP3 expression as an independent prognostic marker for metastatic progression and death for patients with clear cell renal cell carcinoma. Cancer. 2008;112:1471–9.

    Article  PubMed  Google Scholar 

  14. Zheng W, Yi X, Fadare O, et al. The oncofetal protein IMP3: a novel biomarker for endometrial serous carcinoma. Am J Surg Pathol. 2008;32:304–15.

    Article  PubMed  Google Scholar 

  15. Sitnikova L, Mendese G, Liu Q, et al. IMP3 predicts aggressive superficial urothelial carcinoma of the bladder. Clin Cancer Res. 2008;14:1701–6.

    Article  PubMed  CAS  Google Scholar 

  16. Jeng YM, Chang CC, Hu FC, et al. Expression of RNA-binding protein IMP-3 promotes tumor invasion and predicts high tumor stage, early tumor recurrence, and poor prognosis in hepatocellular carcinoma. Hepatology. 2008;48:1118–27.

    Article  PubMed  CAS  Google Scholar 

  17. Mueller-Pillasch F, Lacher U, Wallrapp C, et al. Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain containing protein. Oncogene. 1997;14:2729–33.

    Article  PubMed  CAS  Google Scholar 

  18. Liao B, Hu Y, Herrick DJ, Brewer G. The RNA-binding protein IMP-3 is a translational activator of insulin-like growth factor II leader-3 mRNA during proliferation of human K562 leukemia cells. J Biol Chem. 2005;280:18517–24.

    Article  PubMed  CAS  Google Scholar 

  19. O’Connell JB, Maggard MA, Ko CY. Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst. 2004;96:1420–5.

    Article  PubMed  Google Scholar 

  20. Wang J, Hassett JM, Dayton MT, Kulaylat MN. Lymph node ratio: role in the staging of node-positive colon cancer. Ann Surg Oncol. 2008;15:1600–8.

    Article  PubMed  Google Scholar 

  21. Greene FL, Page DL, Fleming ID, et al. AJCC Cancer Staging Manual. 6th ed. New York: Springer-Verlag, 2002.

    Google Scholar 

  22. Nelson H, Petrelli N, Carlin A, et al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst. 2001;93:583–96.

    Article  PubMed  CAS  Google Scholar 

  23. Tepper JE, O’Connell MJ, Niedzwiecki D, et al. Impact of number of nodes retrieved on outcome in patients with rectal cancer. J Clin Oncol. 2001;19:157–63.

    PubMed  CAS  Google Scholar 

  24. Le Voyer TE, Sigurdson ER, Hanlon AL, et al. Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089. J Clin Oncol. 2003;21:2912–9.

    Article  PubMed  CAS  Google Scholar 

  25. Berger AC, Sigurdson ER, LeVoyer T, et al. Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol. 2005;23:8706–12.

    Article  PubMed  Google Scholar 

  26. Telian SH, Bilchik AJ. Significance of the lymph node ratio in stage III colon cancer. Ann Surg Oncol. 2008;15:1557–8.

    Article  PubMed  Google Scholar 

  27. Megale Costa LJ, Soares HP, Gaspar HA, et al. Ratio between positive lymph nodes and total dissected axillaries lymph nodes as an independent prognostic factor for disease-free survival in patients with breast cancer. Am J Clin Oncol. 2004;27:304–6.

    Article  PubMed  Google Scholar 

  28. Woodward WA, Vinh-Hung V, Ueno NT, et al. Prognostic value of nodal ratios in node-positive breast cancer. J Clin Oncol. 2006;24:2910–6.

    Article  PubMed  Google Scholar 

  29. Siewert JR, Böttcher K, Stein HJ, Roder JD. Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study. Ann Surg. 1998;228:449–61.

    Article  PubMed  CAS  Google Scholar 

  30. Inoue K, Nakane Y, Iiyama H, et al. The superiority of ratio-based lymph node staging in gastric carcinoma. Ann Surg Oncol. 2002;9:27–34.

    Article  PubMed  Google Scholar 

  31. Slidell MB, Chang DC, Cameron JL, et al. Impact of total lymph node count and lymph node ratio on staging and survival after pancreatectomy for pancreatic adenocarcinoma: a large, population-based analysis. Ann Surg Oncol. 2008;15:165–74.

    Article  PubMed  Google Scholar 

  32. Schumacher P, Dineen S, Barnett C Jr., Fleming JTA. The metastatic lymph node ratio predicts survival in colon cancer. Am J Surg Pathol. 2007;194:827–31.

    Google Scholar 

  33. Lee HY, Choi HJ, Park KJ, et al. Prognostic significance of metastatic lymph node ratio in node-positive colon carcinoma. Ann Surg Oncol. 2007;14:1712–7.

    Article  PubMed  Google Scholar 

  34. Jeng YM, Wang TH, Lu SH, Yuan RH, Hsu HC. Prognostic significance of insulin-like growth factor II mRNA-binding protein 3 expression in gastric adenocarcinoma. Br J Surg. 2008;96:66–73.

    Article  CAS  Google Scholar 

  35. De Ridder M, Vinh-Hung V, Van Nieuwenhove Y, et al. Prognostic value of the lymph node ratio in node positive colon cancer. Gut. 2006;55:1681.

    Google Scholar 

  36. Vikesaa J, Hansen TV, Jonson L, et al. RNA-binding IMPs promote cell adhesion and invadopodia formation. EMBO J. 2006;25:1456–68.

    Article  PubMed  CAS  Google Scholar 

  37. Yaniv K, Fainsod A, Kalcheim C, Yisraeli JK. The RNA-binding protein Vg1 RBP is required for cell migration during early neural development. Development. 2003;130:5649–61.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by a grant from the Tao-Yuan General Hospital, Department of Health, Executive Yuan, R.O.C. (PTH9701 to R.H.Y.). We thank Hong-I Hsu for her technical assistance.

Author information

Authors and Affiliations

  1. Department of Surgery, Tao-Yuan General Hospital, Department of Health, Executive Yuan, R.O.C., Tao-Yuan, Taiwan

    Ray-Hwang Yuan MD, PhD, Chi-Chao Wang MD & Chia-Cheng Chou MD

  2. Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan

    Yung-Ming Jeng MD, PhD

  3. Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

    Ray-Hwang Yuan MD, PhD, King-Jen Chang MD, PhD & Po-Huang Lee MD

  4. Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan

    Yung-Ming Jeng MD, PhD

  5. Department of Surgery, College of Medicine, National Taiwan University, Taipei, Taiwan

    Ray-Hwang Yuan MD, PhD, King-Jen Chang MD, PhD & Po-Huang Lee MD

Authors
  1. Ray-Hwang Yuan MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chi-Chao Wang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chia-Cheng Chou MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. King-Jen Chang MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Po-Huang Lee MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yung-Ming Jeng MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yung-Ming Jeng MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yuan, RH., Wang, CC., Chou, CC. et al. Diffuse Expression of RNA-Binding Protein IMP3 Predicts High-Stage Lymph Node Metastasis and Poor Prognosis in Colorectal Adenocarcinoma. Ann Surg Oncol 16, 1711–1719 (2009). https://doi.org/10.1245/s10434-009-0446-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-009-0446-0

Keywords

Search

Navigation