L1CAM Predicts Recurrence and Poor Outcome in Early-stage Type I Endometrial Cancer
Although patients with early-stage type I endometrial cancer have very good prognosis, a substantial proportion experience recurrence and die from the disease. In a study published in Journal of the National Cancer Institute, Alain G. Zeimet, MD, PhD, of Innsbruck Medical University, Austria, and colleagues assessed the ability of L1 cell adhesion molecule (L1CAM) expression to discriminate patients with poorer outcome in a population of patients with Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) stage I, type I endometrioid endometrial carcinomas. Their findings indicate that L1CAM is a powerful predictor of poor outcome and suggest that patients with L1CAM-positive disease should receive adjuvant therapy.
In this retrospective multicenter cohort study, tumor specimens from 1,021 patients were assessed for L1CAM expression by immunohistochemistry, and associations between L1CAM expression and disease-free survival and overall survival were analyzed.
Factors Associated with L1CAM Positivity
Of the 1,021 patients (median age at diagnosis, 64 years), 181 (17.7%) were found to have L1CAM-positive tumors. Overall, 96.4% of the cancers were purely endometrioid and 3.6% showed areas of nonendometrioid differentiation; cancers containing a second cell type were more frequently L1CAM-positive than were purely endometrioid tumors (P = .003). Stage IB cancers were also more frequently L1CAM-positive than were stage IA cancers (P < .001).
L1CAM status was not associated with patient age at diagnosis or to such classical risk factors as diabetes, obesity, nulliparity, hypertension, and unopposed estrogen exposure. According to classical risk assessment, 13.2% of low-risk cancers were L1CAM-positive, compared with 25.8% of intermediate- and high-risk cancers (P < .001). L1CAM positivity was also associated with histopathologic grade (P < .001) and increasing depth of myometrium infiltration (P < .001).
Reduced Survival
Over a median follow-up of 5.3 years, 117 patients (11.5%) had recurrences, with recurrence being observed in 51.4% of patients with L1CAM-positive tumors and in 2.9% of those with L1CAM-negative tumors. On univariate analyses, median disease-free survival (4.5 years vs not reached) and overall survival (8.9 years vs not reached) were significantly poorer in patients with L1CAM-positive cancers (both P < .001).
Powerful Predictive Strength
In multivariable analysis including histology, age at diagnosis, stage, risk assessment (low vs intermediate/high), and grade, L1CAM expression retained independent prognostic significance for disease-free survival (hazard ratio [HR] = 16.33, P < .001) and overall survival (HR = 15.01, P < .001). L1CAM positivity was also independently predictive of both locoregional recurrence (HR = 13.37, P < .001) and distant recurrence (HR = 34.07, P < .001). For L1CAM-negative cancers, grading and risk assessment were irrelevant for predicting disease-free survival and overall survival, with the prognostic relevance of these parameters being related strictly to L1CAM positivity.
A classification and regression decision tree analysis identified L1CAM as the best variable for predicting recurrence and death within 5 years, with sensitivity of 0.74 and specificity of 0.91 (accuracy, 87.9%) for recurrence and sensitivity of 0.77 and specificity of 0.89 (accuracy, 87.6%) for death.
The investigators concluded, “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.” They further noted that L1CAM may serve as a treatment target and that their research group currently is developing a humanized anti-L1CAM antibody for clinical use.
The study was supported by Verein zur Krebsforschung in der Frauenheilkunde, Innsbruck, Austria.
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