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

Autor: Ulla Puistola, Léon C van Kempen, Samira Abdel Azim, Uwe Schirmer, Frédéric Amant, Johan Bulten, Alexandra Meuter, Stephan Polterauer, Elisabeth Müller-Holzner, Elisa Lappi-Blanco, Alon Ben-Arie, Stephan W Jahn, Staci Tanouye, Andrea Mariani, Peter Oppelt, Leon F.A.G. Massuger, Alain G. Zeimet, Monika Stroh-Weigert, Monica Huszar, Mina Fogel, Ignace Vergote, Peter Altevogt, Daniel Reimer, Christian Marth, Yvette P. Geels, Boris Winterhoff, Michael Netzer, Alexander Reinthaller, Werner O. Hackl, Edgar Petru
Přispěvatelé: Other departments
Rok vydání: 2013
Předmět:
Adult
Oncology
Cancer Research
medicine.medical_specialty
Ovariectomy
Brachytherapy
Neural Cell Adhesion Molecule L1
Kaplan-Meier Estimate
Aetiology
screening and detection [ONCOL 5]
Hysterectomy
Risk Assessment
Sensitivity and Specificity
Disease-Free Survival
Salpingectomy
Predictive Value of Tests
Translational research [ONCOL 3]
Internal medicine
Biomarkers
Tumor
Humans
Medicine
Aged
Neoplasm Staging
Proportional Hazards Models
Retrospective Studies
Framingham Risk Score
Hereditary cancer and cancer-related syndromes [ONCOL 1]
business.industry
Proportional hazards model
Endometrial cancer
Hazard ratio
Retrospective cohort study
Middle Aged
medicine.disease
Immunohistochemistry
Aetiology
screening and detection Immune Regulation [ONCOL 5]
Confidence interval
Endometrial Neoplasms
Surgery
Predictive value of tests
Multivariate Analysis
Lymph Node Excision
Female
Radiotherapy
Adjuvant
Neoplasm Recurrence
Local
business
Cohort study
Zdroj: Journal of the National Cancer Institute, 105, 1142-1150
Journal of the National Cancer Institute, 105, 15, pp. 1142-1150
Journal of the National Cancer Institute, 105(15), 1142-1150. Oxford University Press
ISSN: 1460-2105
0027-8874
1142-1150
DOI: 10.1093/jnci/djt144
Popis: Contains fulltext : 124525.pdf (Publisher’s version ) (Closed access) BACKGROUND: Despite the excellent prognosis of Federation Internationale de Gynecologie et d'Obstetrique (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.
Databáze: OpenAIRE
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