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

doi:https://doi.org/10.1093/jnci/djt144

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 OppeltMonika Stroh-Weigert, Alexander Reinthaller, Andrea Mariani, Werner Hackl, Michael Netzer, Uwe Schirmer, Ignace Vergote, Peter Altevogt, Christian Marth, Mina Fogel

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Research output: Contribution to journal › Article › Academic › peer-review

182 Citations (Scopus)

Abstract

Despite the excellent prognosis of Fdration Internationale de Gyncologie et dObsttrique (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. We conducted a retrospective multicenter cohort study to determine expression of L1CAM by immunohistochemistry in 1021 endometrial cancer specimens. The KaplanMeier 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. 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). 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

Original language	English
Pages (from-to)	1142-1150
Journal	Journal of the National Cancer Institute
Volume	105
Issue number	15
DOIs	https://doi.org/10.1093/jnci/djt144
Publication status	Published - 2013

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Zeimet, A. G., Reimer, D., Huszar, M., Winterhoff, B., Puistola, U., Azim, S. A., Müller-Holzner, E., Ben-Arie, A., van Kempen, L. C., Petru, E., Jahn, S., Geels, Y. P., Massuger, L. F., Amant, F., Polterauer, S., Lappi-Blanco, E., Bulten, J., Meuter, A., Tanouye, S., ... Fogel, M. (2013). L1CAM in Early-Stage Type I Endometrial Cancer: Results of a Large Multicenter Evaluation. Journal of the National Cancer Institute, 105(15), 1142-1150. https://doi.org/10.1093/jnci/djt144

@article{f0de32086e484b5daa962f4e12005379,

title = "L1CAM in Early-Stage Type I Endometrial Cancer: Results of a Large Multicenter Evaluation",

abstract = "Despite the excellent prognosis of Fdration Internationale de Gyncologie et dObsttrique (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. We conducted a retrospective multicenter cohort study to determine expression of L1CAM by immunohistochemistry in 1021 endometrial cancer specimens. The KaplanMeier 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. 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). 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",

author = "Zeimet, {Alain G.} and Daniel Reimer and Monica Huszar and Boris Winterhoff and Ulla Puistola and Azim, {Samira Abdel} and Elisabeth M{\"u}ller-Holzner and Alon Ben-Arie and {van Kempen}, {L{\'e}on C.} and Edgar Petru and Stephan Jahn and Geels, {Yvette P.} and Massuger, {Leon F.} and Fr{\'e}d{\'e}ric Amant and Stephan Polterauer and Elisa Lappi-Blanco and Johan Bulten and Alexandra Meuter and Staci Tanouye and Peter Oppelt and Monika Stroh-Weigert and Alexander Reinthaller and Andrea Mariani and Werner Hackl and Michael Netzer and Uwe Schirmer and Ignace Vergote and Peter Altevogt and Christian Marth and Mina Fogel",

year = "2013",

doi = "https://doi.org/10.1093/jnci/djt144",

language = "English",

volume = "105",

pages = "1142--1150",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "15",

}

Zeimet, AG, Reimer, D, Huszar, M, Winterhoff, B, Puistola, U, Azim, SA, Müller-Holzner, E, Ben-Arie, A, van Kempen, LC, Petru, E, Jahn, S, Geels, YP, Massuger, LF, Amant, F, Polterauer, S, Lappi-Blanco, E, Bulten, J, Meuter, A, Tanouye, S, Oppelt, P, Stroh-Weigert, M, Reinthaller, A, Mariani, A, Hackl, W, Netzer, M, Schirmer, U, Vergote, I, Altevogt, P, Marth, C & Fogel, M 2013, 'L1CAM in Early-Stage Type I Endometrial Cancer: Results of a Large Multicenter Evaluation', Journal of the National Cancer Institute, vol. 105, no. 15, pp. 1142-1150. https://doi.org/10.1093/jnci/djt144

TY - JOUR

T1 - L1CAM in Early-Stage Type I Endometrial Cancer: 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

PY - 2013

Y1 - 2013

N2 - Despite the excellent prognosis of Fdration Internationale de Gyncologie et dObsttrique (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. We conducted a retrospective multicenter cohort study to determine expression of L1CAM by immunohistochemistry in 1021 endometrial cancer specimens. The KaplanMeier 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. 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). 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

AB - Despite the excellent prognosis of Fdration Internationale de Gyncologie et dObsttrique (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. We conducted a retrospective multicenter cohort study to determine expression of L1CAM by immunohistochemistry in 1021 endometrial cancer specimens. The KaplanMeier 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. 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). 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

U2 - https://doi.org/10.1093/jnci/djt144

DO - https://doi.org/10.1093/jnci/djt144

M3 - Article

C2 - 23781004

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 -