Skip to main content
Top
Published in: Annals of Surgical Oncology 6/2009

01-06-2009 | Translational Research and Biomarkers

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

Authors: Ray-Hwang Yuan, MD, PhD, Chi-Chao Wang, MD, Chia-Cheng Chou, MD, King-Jen Chang, MD, PhD, Po-Huang Lee, MD, Yung-Ming Jeng, MD, PhD

Published in: Annals of Surgical Oncology | Issue 6/2009

Login to get access

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.
Literature
1.
go back to reference Zlobec I, Lugli A. Prognostic and predictive factors in colorectal cancer. J Clin Pathol. 2008;61:561–9.PubMed Zlobec I, Lugli A. Prognostic and predictive factors in colorectal cancer. J Clin Pathol. 2008;61:561–9.PubMed
2.
go back to reference 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 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
3.
go back to reference Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82:4–6.PubMedCrossRef Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82:4–6.PubMedCrossRef
4.
go back to reference 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 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
5.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
6.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
7.
go back to reference 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 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
8.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
9.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
10.
go back to reference Gress TM, Muller-Pillasch F, Geng M, et al. A pancreatic cancer-specific expression profile. Oncogene. 1996;13:1819–930.PubMed Gress TM, Muller-Pillasch F, Geng M, et al. A pancreatic cancer-specific expression profile. Oncogene. 1996;13:1819–930.PubMed
11.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
12.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
13.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
14.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
15.
go back to reference Sitnikova L, Mendese G, Liu Q, et al. IMP3 predicts aggressive superficial urothelial carcinoma of the bladder. Clin Cancer Res. 2008;14:1701–6.PubMedCrossRef Sitnikova L, Mendese G, Liu Q, et al. IMP3 predicts aggressive superficial urothelial carcinoma of the bladder. Clin Cancer Res. 2008;14:1701–6.PubMedCrossRef
16.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
17.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
18.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
21.
go back to reference Greene FL, Page DL, Fleming ID, et al. AJCC Cancer Staging Manual. 6th ed. New York: Springer-Verlag, 2002. Greene FL, Page DL, Fleming ID, et al. AJCC Cancer Staging Manual. 6th ed. New York: Springer-Verlag, 2002.
22.
go back to reference Nelson H, Petrelli N, Carlin A, et al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst. 2001;93:583–96.PubMedCrossRef Nelson H, Petrelli N, Carlin A, et al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst. 2001;93:583–96.PubMedCrossRef
23.
go back to reference 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 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
24.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
25.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
26.
go back to reference Telian SH, Bilchik AJ. Significance of the lymph node ratio in stage III colon cancer. Ann Surg Oncol. 2008;15:1557–8.PubMedCrossRef Telian SH, Bilchik AJ. Significance of the lymph node ratio in stage III colon cancer. Ann Surg Oncol. 2008;15:1557–8.PubMedCrossRef
27.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
28.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
29.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
30.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
31.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
32.
go back to reference 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. 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.
33.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
34.
go back to reference 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.CrossRef 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.CrossRef
35.
go back to reference 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. 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.
36.
go back to reference Vikesaa J, Hansen TV, Jonson L, et al. RNA-binding IMPs promote cell adhesion and invadopodia formation. EMBO J. 2006;25:1456–68.PubMedCrossRef Vikesaa J, Hansen TV, Jonson L, et al. RNA-binding IMPs promote cell adhesion and invadopodia formation. EMBO J. 2006;25:1456–68.PubMedCrossRef
37.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
Metadata
Title
Diffuse Expression of RNA-Binding Protein IMP3 Predicts High-Stage Lymph Node Metastasis and Poor Prognosis in Colorectal Adenocarcinoma
Authors
Ray-Hwang Yuan, MD, PhD
Chi-Chao Wang, MD
Chia-Cheng Chou, MD
King-Jen Chang, MD, PhD
Po-Huang Lee, MD
Yung-Ming Jeng, MD, PhD
Publication date
01-06-2009
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 6/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0446-0

Other articles of this Issue 6/2009

Annals of Surgical Oncology 6/2009 Go to the issue

EDUCATIONAL REVIEW– TRANSLATIONAL RESEARCH AND BIOMARKERS

Pathologic Response to Preoperative Therapy: Does It Mean What We Think It Means?