By Robert Saunders
NEW YORK (Reuters Health) Jul 11 - When the cell adhesion molecule L1CAM is expressed in early-stage endometrial tumors, there is a 50% chance of recurrence, a multicenter study has shown.
Furthermore, "This adhesion molecule might serve as a treatment target for the fully humanized anti-L1CAM antibody currently under development for clinical use," the researchers say.
Writing in the Journal of the National Cancer Institute online June 18, they explain that type I tumors make up 80% of endometrial cancers, and in the early stage have an excellent prognosis with risk-adapted treatment. However, despite optimal treatment, recurrence and death occur in a "substantial" number of cases.
Based on prior evidence that L1CAM (also termed CD171) may be associated with aggressive tumors, the authors conducted a retrospective analysis of L1CAM expression in 1,021 paraffin-embedded specimens of stage I, type I endometrial cancer in relation to clinical outcomes.
Dr. Alain G. Zeimet, at Innsbruck Medical University, Austria, and colleagues found that 17.7% of the specimens were positive for L1CAM. During a median follow-up of 5.3 years, recurrence rates were 51.4% among the L1CAM-positive cases compared to just 2.9% when cancers were negative for L1CAM. Median overall survival was 8.9 years in patients with L1CAM-positve tumors, whereas median survival has not been reached in the L1CAM-negative patients.
On multivariate analysis, these figures translated to hazard ratios of 16.33 for recurrence and 15.01 for death with L1CAM-positve cancers, according to the report.
The researchers conclude that L1CAM is the best prognostic factor in stage I, type I endometrial cancer so far published. It had sensitivities of 0.74 for recurrence and 0.77 for death, and specificities of 0.91 and 0.89, respectively.
"Moreover," Dr. Zeimet added in an email to Reuters Health, "our data reveal that expression of L1CAM is by far more reliable than FIGO stage (subdivision FIGO-stage Ia and Ib) histopathological grading and is even superior to the currently used standard multifactor risk score in predicting the chance for recurrence and death in early-stage type I endometrial cancer. Of special note is that the power to predict distant recurrences was still more prominent with an extremely high HR of 34.07."
Dr. Zeimet said L1CAM testing is now "essential for routine risk assessment in early type I endometrial cancer."
In fact, he commented, L1CAM determination can be easily performed. "A standardized method for fully automated determination by usual equipment and by using commercially available monoclonal antibodies has been developed and validated by Mina Fogel from the Department of Pathology, Kaplan Medical Centre, Rehovot, Israel, (senior author of the paper). This highly reliable method is currently under publication."
L1CAM positivity has implication for treatment, Dr. Zeimet pointed out. "Patients with L1CAM-positive endometrial cancers need an additional adjuvant treatment to improve their clinical outcome."
However, he noted, the best adjuvant treatment for L1CAM positive cancers is still unclear. "To investigate whether or not chemotherapy is an appropriate option to ameliorate the outcome of concerned early stage endometrial cancer patients, an international randomized multicenter trial will start at the end of 2013. In the participating 60 centers, L1CAM will be determined in all type I early endometrial cancers and 330 patients with L1CAM-positive cancers will be randomized 1:1 in an experimental arm (n=165) receiving four cycles of chemotherapy consisting of a carboplatin/liposomal doxorubicin combination. The remaining 165 L1CAM-positive patients will serve as an observational control arm."
Meanwhile, a promising approach could be to use L1CAM itself as a target for antibody-mediated therapy. "A fully humanized anti-L1CAM antibody has been successfully synthesized and tested. The current development of this treatment option is directed by Peter Altevogt (co-author of the paper) from the German Cancer Research Center, in Heidelberg," Dr. Zeimet explained. "Nonetheless, at the moment this humanized L1CAM mab is rather far away from a use in clinical routine."
J Natl Cancer Inst 2013.
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