title: L1 cell adhesion molecule is a strong predictor for distant recurrence and overall survival in early stage endometrial cancer: pooled PORTEC trial results.
abstract: BACKGROUND
  L1 cell adhesion molecule (L1CAM) expression has been implicated as risk factor for disease recurrence in endometrial cancer (EC), most likely due to its role in promoting tumour cell motility. We tested the performance of L1CAM expression in predicting the risk of recurrence in the randomised post operative radiation therapy in endometrial carcinoma (PORTEC)-1 and -2 trials.
  
  
  METHODS
  In the PORTEC trials, stage I EC patients were randomised to external beam radiotherapy (EBRT) versus no additional treatment (PORTEC-1, n=714), or to EBRT versus vaginal brachytherapy (PORTEC-2, n=427). Tumour samples of 865 (75.8%) patients were available for L1CAM expression analysis by immunohistochemistry. An established scoring system for EC was used, with >10% L1CAM staining defined as positive.
  
  
  RESULTS
  Positive L1CAM expression was significantly correlated with risk of distant recurrence, with a hazard ratio (HR) of 5.1 (95% confidence interval (CI) 3.1-8.7) but not with vaginal relapse, while a trend for pelvic nodal relapse was found. Tumours with the highest expression levels (>50% positive) had the strongest risk of distant recurrence (HR 5.3, CI 2.7-10.4). In multivariate Cox analysis with the risk factors age, depth of invasion, grade, lympho-vascular space invasion (LVSI) and treatment, L1CAM expression remained an independent prognostic factor for distant recurrence (HR 3.5, CI 1.92-6.30) and overall survival (HR 2.1, CI 1.41-2.98).
  
  
  CONCLUSIONS
  L1CAM expression is a strong independent predictor for distant recurrence and overall survival in stage I endometrial cancer. These results warrant prospective validation of L1CAM as marker for selecting patients who could benefit from more extensive diagnostic and/or therapeutic procedures.
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: T.Bosse@lumc.nl.
authors.forename: T
authors.initials: T
authors.lastname: Bosse
authors.affiliation: Department of Medical and Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: Nout
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Stelloo
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Dreef
authors.affiliation: Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: H W
authors.initials: HW
authors.lastname: Nijman
authors.affiliation: Department of Radiation Oncology, University Medical Center Utrecht, The Netherlands.
authors.forename: I M
authors.initials: IM
authors.lastname: Jürgenliemk-Schulz
authors.affiliation: Department of Radiotherapy, Medisch Spectrum Twente, Enschede, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Jobsen
authors.affiliation: Department of Medical and Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: C L
authors.initials: CL
authors.lastname: Creutzberg
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: V T H B M
authors.initials: VT
authors.lastname: Smit
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism*; D009367:Neoplasm Staging; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D011184:Postoperative Period; D011237:Predictive Value of Tests; D011379:Prognosis; D011878:Radiotherapy / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D039842:Neural Cell Adhesion Molecule L1
keywords: Endometrial cancer; L1CAM; PORTEC; Prognostic marker