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.
Similar content being viewed by others
References
Sung JJ, Lau JY, Goh KL, Leung WK. Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncol 2005; 6:871–6
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 376–7
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; 23:721–6
Hortsch M. Structural and functional evolution of the L1 family: are four adhesion molecules better than one? Mol Cell Neurosci 2000; 15:1–10
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; 279:28880–8
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; 38:1708–16
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; 115:658–65
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; 11:1190–7
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; 362:869–75
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; 56:1440–4
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; 28:359–68
Kolligs FT, Bommer G, Goke B. Wnt/beta-catenin/tcf signaling: a critical pathway in gastrointestinal tumorigenesis. Digestion 2002; 66:131–44
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; 168:633–42
Ikeguchi M, Makino M, Kaibara N. Clinical significance of E-cadherin-catenin complex expression in metastatic foci of colorectal carcinoma. J Surg Oncol 2001; 77:201–7
Beavon IR. The E-cadherin–catenin complex in tumour metastasis: structure, function and regulation. Eur J Cancer 2000; 36:1607–20
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; 35:60–5
Takayama T, Shiozaki H, Doki Y, et al. Aberrant expression and phosphorylation of beta-catenin in human colorectal cancer. Br J Cancer 1998; 77:605–13
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; 111:921–8
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; 111:29–37
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; 163:847–57
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; 155:661–73
Meier F, Busch S, Gast D, et al. The adhesion molecule L1 (CD171) promotes melanoma progression. Int J Cancer 2006; 119:549–55
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; 66:936–43
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Boo, YJ., Park, JM., Kim, J. et al. L1 Expression as a Marker for Poor Prognosis, Tumor Progression, and Short Survival in Patients with Colorectal Cancer. Ann Surg Oncol 14, 1703–1711 (2007). https://doi.org/10.1245/s10434-006-9281-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-006-9281-8