title: 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.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. jkaifi@uke.uni-hamburg.de
authors.forename: Jussuf T
authors.initials: JT
authors.lastname: Kaifi
authors.forename: Uta
authors.initials: U
authors.lastname: Reichelt
authors.forename: Alexander
authors.initials: A
authors.lastname: Quaas
authors.forename: Paulus G
authors.initials: PG
authors.lastname: Schurr
authors.forename: Robin
authors.initials: R
authors.lastname: Wachowiak
authors.forename: Emre F
authors.initials: EF
authors.lastname: Yekebas
authors.forename: Tim
authors.initials: T
authors.lastname: Strate
authors.forename: Claus
authors.initials: C
authors.lastname: Schneider
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D039842:Neural Cell Adhesion Molecule L1 / Q000096:biosynthesis*; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D039842:Neural Cell Adhesion Molecule L1