L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas

Background: Ovarian and uterine carcinomas are the most common cause of cancer-related deaths in gynecological malignant diseases. We aimed to assess whether the L1 adhesion molecule, an important mediator for cell migration for neural and tumour cells, is expressed in these carcinomas. Methods: We investigated L1 expression by immunohistochemistry, RT-PCR, and Western blot analysis of tumour samples. Soluble L1 in the serum was detected by ELISA and immunoprecipitation. Findings: We detected the L1 adhesion molecule in ovarian and uterine tumours in a stage-dependent manner. In a retrospective study L1 was found in 46 of 58 ovarian carcinomas and 20 of 72 uterine adenocarcinomas. L1 expression was an excellent predictor of poor outlook (p<0·00001). Patients with L1 positive uterine tumours were at high risk for progression even in the endometrioid-type tumours, which usually have a favourable prognosis. In uterine tumours, expression of L1 in curettage samples enabled us to identify aggressive tumours before the operation. Soluble L1 was specifically detected in serum samples from patients with ovarian and uterine tumours. ADAM10, which was implicated in previous studies as L1 sheddase, was expressed in tumours in which soluble L1 was present in the serum. Interpretation: L1 is overexpressed in ovarian and uterine carcinomas and is associated with short survival. L1 can serve as a new marker for prediction of clinical outcome and could be helpful to identify patients with uterine tumours who are at high risk for recurrent disease. L1 expression and cleavage could promote dissemination of tumours by facilitating cell migration.