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

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

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1183-1190
Number of pages8
JournalModern Pathology
Volume20
Issue number11
DOIs
StatePublished - Nov 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Keywords

  • Colorectal cancer
  • L1 cell adhesion molecule
  • Micrometastasis

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