L1CAM in early-stage type I endometrial cancer: results of a large multicenter evaluation

Alain G Zeimet, Daniel Reimer, Monica Huszar, Boris Winterhoff, Ulla Puistola, Samira Abdel Azim, Elisabeth Müller-Holzner, Alon Ben-Arie, Léon C van Kempen, Edgar Petru, Stephan Jahn, Yvette P Geels, Leon F Massuger, Frédéric Amant, Stephan Polterauer, Elisa Lappi-Blanco, Johan Bulten, Alexandra Meuter, Staci Tanouye, Peter Oppelt, Monika Stroh-Weigert, Alexander Reinthaller, Andrea Mariani, Werner Hackl, Michael Netzer, Uwe Schirmer, Ignace Vergote, Peter Altevogt, Christian Marth, Mina Fogel
Journal of the National Cancer Institute 2013 August 7, 105 (15): 1142-50

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.

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