Skip to main content
Top
Published in: Annals of Surgical Oncology 5/2007

01-05-2007

L1 Expression as a Marker for Poor Prognosis, Tumor Progression, and Short Survival in Patients with Colorectal Cancer

Authors: Yoon-Jung Boo, MD, Joong-Min Park, MD, Jin Kim, MD, Yang-Seok Chae, MD, Byung-Wook Min, MD, Jun-Won Um, MD, Hong-Young Moon, MD

Published in: Annals of Surgical Oncology | Issue 5/2007

Login to get access

Abstract

Background

L1, a new target gene for Wnt/β-catenin–TCF signaling, has been identified in the invasive front of colorectal cancer cells in vitro study. The L1 molecule is localized on the cell surface in tumor tissues, accompanied with loss of β-catenin and E-cadherin. However, such association between L1 expression and prognosis of colorectal cancer has not yet been investigated in clinical study. We investigated the expression of L1, E-cadherin, and β-catenin in tumor cells to determine correlations between the clinicopathologic characteristics and the expression of these molecules and to evaluate the efficacy of the use of these molecules as prognostic markers for patient survival.

Methods

We investigated 138 patients who received diagnoses of colorectal cancer and who underwent surgery between January 1995 and December 2000 at the Korea University Hospital. Tissues were obtained from paraffin-embedded blocks of the tumors and studied by tissue microarray analysis. Immunohistochemical staining for L1, β-catenin, and E-cadherin was performed for each specimen.

Results

L1 expression was found to be correlated with advanced cancer stage (P = .001), distant metastasis (P < .001), and tumor recurrence (P = .006). Survival analysis showed that reduced expression of β-catenin and E-cadherin, and expression of L1 were statistically significantly related to poor survival. Multivariate analysis revealed that L1 expression was an independent prognostic factor for patient survival.

Conclusions

L1 expression is associated with tumor progression and poor survival in patients with colorectal cancer and may be clinically useful as a marker for poor prognosis.
Literature
1.
go back to reference Sung JJ, Lau JY, Goh KL, Leung WK. Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncol 2005; 6:871–6PubMedCrossRef Sung JJ, Lau JY, Goh KL, Leung WK. Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncol 2005; 6:871–6PubMedCrossRef
2.
go back to reference Hernanz F, Revuelta S, Redondo C, Madrazo C, Castillo J, Gomez-Fleitas M. Colorectal adenocarcinoma: quality of the assessment of lymph node metastases. Dis Colon Rectum 1994; 37:373–6; discussion 376–7PubMedCrossRef Hernanz F, Revuelta S, Redondo C, Madrazo C, Castillo J, Gomez-Fleitas M. Colorectal adenocarcinoma: quality of the assessment of lymph node metastases. Dis Colon Rectum 1994; 37:373–6; discussion 376–7PubMedCrossRef
3.
go back to reference Park YJ, Park KJ, Park JG, Lee KU, Choe KJ, Kim JP. Prognostic factors in 2230 Korean colorectal cancer patients: analysis of consecutively operated cases. World J Surg 1999; 23:721–6PubMedCrossRef Park YJ, Park KJ, Park JG, Lee KU, Choe KJ, Kim JP. Prognostic factors in 2230 Korean colorectal cancer patients: analysis of consecutively operated cases. World J Surg 1999; 23:721–6PubMedCrossRef
4.
go back to reference Hortsch M. Structural and functional evolution of the L1 family: are four adhesion molecules better than one? Mol Cell Neurosci 2000; 15:1–10PubMedCrossRef Hortsch M. Structural and functional evolution of the L1 family: are four adhesion molecules better than one? Mol Cell Neurosci 2000; 15:1–10PubMedCrossRef
5.
go back to reference Silletti S, Yebra M, Perez B, Cirulli V, McMahon M, Montgomery AM. Extracellular signal-regulated kinase (ERK)-dependent gene expression contributes to L1 cell adhesion molecule-dependent motility and invasion. J Biol Chem 2004; 279:28880–8PubMedCrossRef Silletti S, Yebra M, Perez B, Cirulli V, McMahon M, Montgomery AM. Extracellular signal-regulated kinase (ERK)-dependent gene expression contributes to L1 cell adhesion molecule-dependent motility and invasion. J Biol Chem 2004; 279:28880–8PubMedCrossRef
6.
go back to reference Thies A, Schachner M, Moll I, et al. Overexpression of the cell adhesion molecule L1 is associated with metastasis in cutaneous malignant melanoma. Eur J Cancer 2002; 38:1708–16PubMedCrossRef Thies A, Schachner M, Moll I, et al. Overexpression of the cell adhesion molecule L1 is associated with metastasis in cutaneous malignant melanoma. Eur J Cancer 2002; 38:1708–16PubMedCrossRef
7.
go back to reference Gast D, Riedle S, Riedle S, et al. L1 augments cell migration and tumor growth but not beta3 integrin expression in ovarian carcinomas. Int J Cancer 2005; 115:658–65PubMedCrossRef Gast D, Riedle S, Riedle S, et al. L1 augments cell migration and tumor growth but not beta3 integrin expression in ovarian carcinomas. Int J Cancer 2005; 115:658–65PubMedCrossRef
8.
go back to reference Allory Y, Matsuoka Y, Bazille C, Christensen EI, Ronco P, Debiec H. The L1 cell adhesion molecule is induced in renal cancer cells and correlates with metastasis in clear cell carcinomas. Clin Cancer Res 2005; 11:1190–7PubMed Allory Y, Matsuoka Y, Bazille C, Christensen EI, Ronco P, Debiec H. The L1 cell adhesion molecule is induced in renal cancer cells and correlates with metastasis in clear cell carcinomas. Clin Cancer Res 2005; 11:1190–7PubMed
9.
go back to reference Fogel M, Gutwein P, Mechtersheimer S, et al. L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas. Lancet 2003; 362:869–75PubMedCrossRef Fogel M, Gutwein P, Mechtersheimer S, et al. L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas. Lancet 2003; 362:869–75PubMedCrossRef
10.
go back to reference Izumoto S, Ohnishi T, Arita N, Hiraga S, Taki T, Hayakawa T. Gene expression of neural cell adhesion molecule L1 in malignant gliomas and biological significance of L1 in glioma invasion. Cancer Res 1996; 56:1440–4PubMed Izumoto S, Ohnishi T, Arita N, Hiraga S, Taki T, Hayakawa T. Gene expression of neural cell adhesion molecule L1 in malignant gliomas and biological significance of L1 in glioma invasion. Cancer Res 1996; 56:1440–4PubMed
11.
go back to reference Hoefnagel CA, Rutgers M, Buitenhuis CK, et al. A comparison of targeting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients. Eur J Nucl Med 2001; 28:359–68PubMedCrossRef Hoefnagel CA, Rutgers M, Buitenhuis CK, et al. A comparison of targeting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients. Eur J Nucl Med 2001; 28:359–68PubMedCrossRef
12.
go back to reference Kolligs FT, Bommer G, Goke B. Wnt/beta-catenin/tcf signaling: a critical pathway in gastrointestinal tumorigenesis. Digestion 2002; 66:131–44PubMedCrossRef Kolligs FT, Bommer G, Goke B. Wnt/beta-catenin/tcf signaling: a critical pathway in gastrointestinal tumorigenesis. Digestion 2002; 66:131–44PubMedCrossRef
13.
go back to reference Gavert N, Conacci-Sorrell M, Gast D, et al. L1, a novel target of beta-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers. J Cell Biol 2005; 168:633–42PubMedCrossRef Gavert N, Conacci-Sorrell M, Gast D, et al. L1, a novel target of beta-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers. J Cell Biol 2005; 168:633–42PubMedCrossRef
14.
go back to reference Ikeguchi M, Makino M, Kaibara N. Clinical significance of E-cadherin-catenin complex expression in metastatic foci of colorectal carcinoma. J Surg Oncol 2001; 77:201–7PubMedCrossRef Ikeguchi M, Makino M, Kaibara N. Clinical significance of E-cadherin-catenin complex expression in metastatic foci of colorectal carcinoma. J Surg Oncol 2001; 77:201–7PubMedCrossRef
15.
go back to reference Beavon IR. The E-cadherin–catenin complex in tumour metastasis: structure, function and regulation. Eur J Cancer 2000; 36:1607–20PubMedCrossRef Beavon IR. The E-cadherin–catenin complex in tumour metastasis: structure, function and regulation. Eur J Cancer 2000; 36:1607–20PubMedCrossRef
16.
go back to reference Ghadimi BM, Behrens J, Hoffmann I, Haensch W, Birchmeier W, Schlag PM. Immunohistological analysis of E-cadherin, alpha-, beta- and gamma-catenin expression in colorectal cancer: implications for cell adhesion and signaling. Eur J Cancer 1999; 35:60–5PubMedCrossRef Ghadimi BM, Behrens J, Hoffmann I, Haensch W, Birchmeier W, Schlag PM. Immunohistological analysis of E-cadherin, alpha-, beta- and gamma-catenin expression in colorectal cancer: implications for cell adhesion and signaling. Eur J Cancer 1999; 35:60–5PubMedCrossRef
17.
go back to reference Takayama T, Shiozaki H, Doki Y, et al. Aberrant expression and phosphorylation of beta-catenin in human colorectal cancer. Br J Cancer 1998; 77:605–13PubMed Takayama T, Shiozaki H, Doki Y, et al. Aberrant expression and phosphorylation of beta-catenin in human colorectal cancer. Br J Cancer 1998; 77:605–13PubMed
18.
go back to reference Fernebro E, Bendahl PO, Dictor M, Persson A, Ferno M, Nilbert M. Immunohistochemical patterns in rectal cancer: application of tissue microarray with prognostic correlations. Int J Cancer 2004; 111:921–8PubMedCrossRef Fernebro E, Bendahl PO, Dictor M, Persson A, Ferno M, Nilbert M. Immunohistochemical patterns in rectal cancer: application of tissue microarray with prognostic correlations. Int J Cancer 2004; 111:921–8PubMedCrossRef
19.
go back to reference Gofuku J, Shiozaki H, Tsujinaka T, et al. Expression of E-cadherin and alpha-catenin in patients with colorectal carcinoma. Correlation with cancer invasion and metastasis. Am J Clin Pathol 1999; 111:29–37PubMed Gofuku J, Shiozaki H, Tsujinaka T, et al. Expression of E-cadherin and alpha-catenin in patients with colorectal carcinoma. Correlation with cancer invasion and metastasis. Am J Clin Pathol 1999; 111:29–37PubMed
20.
go back to reference Conacci-Sorrell M, Simcha I, Ben-Yedidia T, Blechman J, Savagner P, Ben-Ze’ev A. Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK. J Cell Biol 2003; 163:847–57PubMedCrossRef Conacci-Sorrell M, Simcha I, Ben-Yedidia T, Blechman J, Savagner P, Ben-Ze’ev A. Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK. J Cell Biol 2003; 163:847–57PubMedCrossRef
21.
go back to reference Mechtersheimer S, Gutwein P, Agmon-Levin N, et al. Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. J Cell Biol 2001; 155:661–73PubMedCrossRef Mechtersheimer S, Gutwein P, Agmon-Levin N, et al. Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. J Cell Biol 2001; 155:661–73PubMedCrossRef
22.
go back to reference Meier F, Busch S, Gast D, et al. The adhesion molecule L1 (CD171) promotes melanoma progression. Int J Cancer 2006; 119:549–55PubMedCrossRef Meier F, Busch S, Gast D, et al. The adhesion molecule L1 (CD171) promotes melanoma progression. Int J Cancer 2006; 119:549–55PubMedCrossRef
23.
go back to reference Arlt MJ, Novak-Hofer I, Gast D, et al. Efficient inhibition of intra-peritoneal tumor growth and dissemination of human ovarian carcinoma cells in nude mice by anti–L1-cell adhesion molecule monoclonal antibody treatment. Cancer Res 2006; 66:936–43PubMedCrossRef Arlt MJ, Novak-Hofer I, Gast D, et al. Efficient inhibition of intra-peritoneal tumor growth and dissemination of human ovarian carcinoma cells in nude mice by anti–L1-cell adhesion molecule monoclonal antibody treatment. Cancer Res 2006; 66:936–43PubMedCrossRef
Metadata
Title
L1 Expression as a Marker for Poor Prognosis, Tumor Progression, and Short Survival in Patients with Colorectal Cancer
Authors
Yoon-Jung Boo, MD
Joong-Min Park, MD
Jin Kim, MD
Yang-Seok Chae, MD
Byung-Wook Min, MD
Jun-Won Um, MD
Hong-Young Moon, MD
Publication date
01-05-2007
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 5/2007
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-006-9281-8

Other articles of this Issue 5/2007

Annals of Surgical Oncology 5/2007 Go to the issue