title: L1CAM in early-stage type I endometrial cancer: results of a large multicenter evaluation.
abstract: BACKGROUND
  Despite the excellent prognosis of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage I, type I endometrial cancers, a substantial number of patients experience recurrence and die from this disease. We analyzed the value of immunohistochemical L1CAM determination to predict clinical outcome.
  
  
  METHODS
  We conducted a retrospective multicenter cohort study to determine expression of L1CAM by immunohistochemistry in 1021 endometrial cancer specimens. The Kaplan-Meier method and Cox proportional hazard model were applied for survival and multivariable analyses. A machine-learning approach was used to validate variables for predicting recurrence and death.
  
  
  RESULTS
  Of 1021 included cancers, 17.7% were rated L1CAM-positive. Of these L1CAM-positive cancers, 51.4% recurred during follow-up compared with 2.9% L1CAM-negative cancers. Patients bearing L1CAM-positive cancers had poorer disease-free and overall survival (two-sided Log-rank P < .001). Multivariable analyses revealed an increase in the likelihood of recurrence (hazard ratio [HR] = 16.33; 95% confidence interval [CI] = 10.55 to 25.28) and death (HR = 15.01; 95% CI = 9.28 to 24.26). In the L1CAM-negative cancers FIGO stage I subdivision, grading and risk assessment were irrelevant for predicting disease-free and overall survival. The prognostic relevance of these parameters was related strictly to L1CAM positivity. A classification and regression decision tree (CRT)identified L1CAM as the best variable for predicting recurrence (sensitivity = 0.74; specificity = 0.91) and death (sensitivity = 0.77; specificity = 0.89).
  
  
  CONCLUSIONS
  To our knowledge, L1CAM has been shown to be the best-ever published prognostic factor in FIGO stage I, type I endometrial cancers and shows clear superiority over the standardly used multifactor risk score. L1CAM expression in type I cancers indicates the need for adjuvant treatment. This adhesion molecule might serve as a treatment target for the fully humanized anti-L1CAM antibody currently under development for clinical use.
authors.affiliation: Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria. alain.zeimet@i-med.ac.at
authors.forename: Alain G
authors.initials: AG
authors.lastname: Zeimet
authors.forename: Daniel
authors.initials: D
authors.lastname: Reimer
authors.forename: Monica
authors.initials: M
authors.lastname: Huszar
authors.forename: Boris
authors.initials: B
authors.lastname: Winterhoff
authors.forename: Ulla
authors.initials: U
authors.lastname: Puistola
authors.forename: Samira Abdel
authors.initials: SA
authors.lastname: Azim
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Müller-Holzner
authors.forename: Alon
authors.initials: A
authors.lastname: Ben-Arie
authors.forename: Léon C
authors.initials: LC
authors.lastname: van Kempen
authors.forename: Edgar
authors.initials: E
authors.lastname: Petru
authors.forename: Stephan
authors.initials: S
authors.lastname: Jahn
authors.forename: Yvette P
authors.initials: YP
authors.lastname: Geels
authors.forename: Leon F
authors.initials: LF
authors.lastname: Massuger
authors.forename: Frédéric
authors.initials: F
authors.lastname: Amant
authors.forename: Stephan
authors.initials: S
authors.lastname: Polterauer
authors.forename: Elisa
authors.initials: E
authors.lastname: Lappi-Blanco
authors.forename: Johan
authors.initials: J
authors.lastname: Bulten
authors.forename: Alexandra
authors.initials: A
authors.lastname: Meuter
authors.forename: Staci
authors.initials: S
authors.lastname: Tanouye
authors.forename: Peter
authors.initials: P
authors.lastname: Oppelt
authors.forename: Monika
authors.initials: M
authors.lastname: Stroh-Weigert
authors.forename: Alexander
authors.initials: A
authors.lastname: Reinthaller
authors.forename: Andrea
authors.initials: A
authors.lastname: Mariani
authors.forename: Werner
authors.initials: W
authors.lastname: Hackl
authors.forename: Michael
authors.initials: M
authors.lastname: Netzer
authors.forename: Uwe
authors.initials: U
authors.lastname: Schirmer
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Peter
authors.initials: P
authors.lastname: Altevogt
authors.forename: Christian
authors.initials: C
authors.lastname: Marth
authors.forename: Mina
authors.initials: M
authors.lastname: Fogel
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001918:Brachytherapy; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000737:chemistry* / Q000175:diagnosis* / Q000401:mortality / Q000517:prevention & control; D009367:Neoplasm Staging; D039842:Neural Cell Adhesion Molecule L1 / Q000032:analysis*; D010052:Ovariectomy; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D018570:Risk Assessment; D058994:Salpingectomy; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D039842:Neural Cell Adhesion Molecule L1