L1 is associated with micrometastatic spread and poor outcome in colorectal cancer.

Abstract

L1 is a cell adhesion molecule expressed at the invasive front of colorectal tumors with an important role in metastasis. The aim of the present study was to determine L1 protein expression in a large cohort of colorectal cancer patients and its impact on early metastatic spread and survival. A total of 375 patients that underwent surgical treatment for colorectal cancer were chosen retrospectively. A tissue microarray was constructed of 576 tissue samples from these patients and analyzed by immunohistochemistry with a monoclonal antibody against human L1 (UJ127). Lymph node and bone marrow micrometastasis were assessed with monoclonal antibodies Ber-EP4 and pancytokeratin A45-B/B3, respectively. Associations between L1 expression and lymph node, bone marrow micrometastasis and survival were investigated with Fisher's, log-rank test and Cox multivariate analysis. All statistical tests were two-sided. L1 was detected in a subset of 48 (13%) of 375 patients examined. Analysis of L1 expression and survival revealed a significantly worse outcome for L1-positive patients by log-rank test (P<0.05). Multivariate Cox regression analysis showed the strongest independent prognostic impact of L1 expression (P<0.05). Fisher's test revealed a significant association of L1 expression and presence of disseminated tumor cells in lymph nodes and bone marrow (P<0.05). L1 is a powerful prognostic marker for patients that undergo complete surgical resection. It may have a role in early metastatic spread, as L1 is associated with micrometastases to both the lymph nodes and bone marrow. Thus, L1 should be explored further as a target for adjuvant therapy for micrometastatic disease.

• Authors: Jussuf T Kaifi, Uta Reichelt, Alexander Quaas, Paulus G Schurr, Robin Wachowiak, Emre F Yekebas, Tim Strate, Claus Schneider, Klaus Pantel, Melitta Schachner, Guido Sauter, Jakob R Izbicki
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 20 Issue 11 Pg. 1183-90 (Nov 2007) ISSN: 0893-3952 [Print] United States
• PMID: 17873897 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Neural Cell Adhesion Molecule L1

Topics

• Adenocarcinoma (metabolism, mortality, pathology)
• Biomarkers, Tumor (analysis)
• Colorectal Neoplasms (metabolism, mortality, pathology)
• Female
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Lymphatic Metastasis (diagnosis)
• Male
• Middle Aged
• Neural Cell Adhesion Molecule L1 (biosynthesis)
• Survival Analysis
• Tissue Array Analysis