Immunohistochemical demonstration of the L1 cell adhesion molecule (L1CAM; CD171) “has been shown to be the best-ever published prognostic factor” in Federation Internationale de Gynecologie et d’Obstetrique (FIGO) stage I, type I endometrial cancers “and shows clear superiority over the standardly used multifactor risk score,” researchers concluded after conducting a retrospective multicenter cohort study. “Of the 1,021 investigated type I endometrial cancers, 17.7% were rated L1CAM-positive in this study. L1CAM expression in 10% or more of the tumor cells was associated with an overwhelming increase in the likelihood of distal or local recurrence and moreover was independently related to poor overall survival,” the researchers reported in the Journal of the National Cancer Institute.
While only 2.9% of L1CAM-negative cancers recurred during follow-up, 51.4% of the L1CAM-positive cancers did. “Patients bearing L1CAM-positive cancers had poorer disease-free and overall survival (two-sided Log-rank P < .001),” the results showed. “Multivariable analyses revealed an increase in the likelihood of recurrence [hazard ratio [HR] = 16.33, 95% confidence interval [CI] = 10.55–25.28] and death [HR = 15.01, 95% CI = 9.28–24.26],” the authors reported.
“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 identified L1CAM as the best variable for predicting recurrence [sensitivity = 0.74, specificity = 0.91] and death [sensitivity = 0.77, specificity = 0.89],” they added.
The authors called for routine immunohistochemical L1CAM determination for all type I endometrial cancers. “It is worth noting that L1CAM-based risk assessment can be obtained from curettage material before major surgery. However, the reliability of this procedure, especially for sampling errors, requires validation in prospective approaches,” the researchers wrote.
“The most intriguing question is what treatment is most beneficial for patients with L1CAM-positive type I endometrial cancers,” the investigators noted. They speculated that chemotherapy could be the most valid option and that another promising approach could be a fully humanized anti-L1CAM antibody currently being developed for clinical use. ■
Zeimet AG, et al: J Natl Cancer Inst 105:1142-1150, 2013.