Fogel Mina, Gutwein Paul, Mechtersheimer Sabine, Riedle Svenja, Stoeck Alexander, Smirnov Asya, Edler Lutz, Ben-Arie Alon, Huszar Monica, Altevogt Peter
Department of Pathology, Kaplan Hospital, Rehovot, Israel.
Lancet. 2003 Sep 13;362(9387):869-75. doi: 10.1016/S0140-6736(03)14342-5.
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.
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.
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.
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.
卵巢癌和子宫癌是妇科恶性疾病中与癌症相关死亡的最常见原因。我们旨在评估L1黏附分子（神经细胞和肿瘤细胞迁移的重要介质）在这些癌症中是否表达。
我们通过免疫组织化学、逆转录聚合酶链反应（RT-PCR）以及肿瘤样本的蛋白质免疫印迹分析来研究L1的表达。通过酶联免疫吸附测定（ELISA）和免疫沉淀法检测血清中的可溶性L1。
我们以分期依赖的方式在卵巢和子宫肿瘤中检测到L1黏附分子。在一项回顾性研究中，58例卵巢癌中有46例、72例子宫腺癌中有20例发现有L1表达。L1表达是预后不良的极佳预测指标（p<0.00001）。即使在通常预后良好的子宫内膜样型肿瘤中，L1阳性子宫肿瘤患者也有很高的进展风险。在子宫肿瘤中，刮宫样本中L1的表达使我们能够在手术前识别侵袭性肿瘤。在卵巢和子宫肿瘤患者的血清样本中特异性检测到可溶性L1。先前研究表明与L1裂解有关的解聚素和金属蛋白酶10（ADAM10）在血清中存在可溶性L1的肿瘤中表达。
L1在卵巢癌和子宫癌中过表达，并与生存期短相关。L1可作为预测临床结局的新标志物，有助于识别子宫肿瘤复发风险高的患者。L1的表达和裂解可通过促进细胞迁移来促进肿瘤播散。
