TY - JOUR
T1 - L1CAM in early-stage type i endometrial cancer
T2 - Results of a large multicenter evaluation
AU - Zeimet, Alain G.
AU - Reimer, Daniel
AU - Huszar, Monica
AU - Winterhoff, Boris
AU - Puistola, Ulla
AU - Azim, Samira Abdel
AU - Müller-Holzner, Elisabeth
AU - Ben-Arie, Alon
AU - Van Kempen, Léon C.
AU - Petru, Edgar
AU - Jahn, Stephan
AU - Geels, Yvette P.
AU - Massuger, Leon F.
AU - Amant, Frédéric
AU - Polterauer, Stephan
AU - Lappi-Blanco, Elisa
AU - Bulten, Johan
AU - Meuter, Alexandra
AU - Tanouye, Staci
AU - Oppelt, Peter
AU - Stroh-Weigert, Monika
AU - Reinthaller, Alexander
AU - Mariani, Andrea
AU - Hackl, Werner
AU - Netzer, Michael
AU - Schirmer, Uwe
AU - Vergote, Ignace
AU - Altevogt, Peter
AU - Marth, Christian
AU - Fogel, Mina
N1 - Funding Information:
This work was supported by Verein zur Krebsforschung in der Frauenheilkunde, Innsbruck, Austria (grant 201023).
PY - 2013/8/7
Y1 - 2013/8/7
N2 - 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.MethodsWe 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.ResultsOf 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).ConclusionsTo 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.
AB - 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.MethodsWe 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.ResultsOf 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).ConclusionsTo 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.
UR - https://www.scopus.com/pages/publications/84881657484
UR - https://www.scopus.com/pages/publications/84881657484#tab=citedBy
U2 - 10.1093/jnci/djt144
DO - 10.1093/jnci/djt144
M3 - Article
C2 - 23781004
AN - SCOPUS:84881657484
SN - 0027-8874
VL - 105
SP - 1142
EP - 1150
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 15
ER -
