Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria.
J Natl Cancer Inst. 2013 Aug 7;105(15):1142-50. doi: 10.1093/jnci/djt144. Epub 2013 Jun 18.
Despite the excellent prognosis of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage I, type I endometrial cancers, a substantial number of patients experience recurrence and die from this disease. We analyzed the value of immunohistochemical L1CAM determination to predict clinical outcome.
We conducted a retrospective multicenter cohort study to determine expression of L1CAM by immunohistochemistry in 1021 endometrial cancer specimens. The Kaplan-Meier method and Cox proportional hazard model were applied for survival and multivariable analyses. A machine-learning approach was used to validate variables for predicting recurrence and death.
Of 1021 included cancers, 17.7% were rated L1CAM-positive. Of these L1CAM-positive cancers, 51.4% recurred during follow-up compared with 2.9% L1CAM-negative cancers. Patients bearing L1CAM-positive cancers had poorer disease-free and overall survival (two-sided Log-rank P < .001). Multivariable analyses revealed an increase in the likelihood of recurrence (hazard ratio [HR] = 16.33; 95% confidence interval [CI] = 10.55 to 25.28) and death (HR = 15.01; 95% CI = 9.28 to 24.26). 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 (CRT)identified L1CAM as the best variable for predicting recurrence (sensitivity = 0.74; specificity = 0.91) and death (sensitivity = 0.77; specificity = 0.89).
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. This adhesion molecule might serve as a treatment target for the fully humanized anti-L1CAM antibody currently under development for clinical use.
尽管国际妇产科联合会（FIGO）I 期、I 型子宫内膜癌的预后极佳，但仍有相当数量的患者复发并因此病死亡。我们分析了免疫组化 L1CAM 检测对预测临床结局的价值。
我们进行了一项回顾性多中心队列研究，以确定 1021 例子宫内膜癌标本中 L1CAM 的免疫组化表达。应用 Kaplan-Meier 法和 Cox 比例风险模型进行生存和多变量分析。采用机器学习方法验证用于预测复发和死亡的变量。
在纳入的 1021 例癌症中，17.7%被评为 L1CAM 阳性。在这些 L1CAM 阳性癌症中，51.4%在随访期间复发，而 L1CAM 阴性癌症的复发率为 2.9%。携带 L1CAM 阳性癌症的患者无病生存率和总生存率较差（双侧 Log-rank P<.001）。多变量分析显示，复发的可能性增加（风险比[HR] = 16.33；95%置信区间[CI] = 10.55 至 25.28）和死亡（HR = 15.01；95%CI = 9.28 至 24.26）。在 L1CAM 阴性的 FIGO I 期亚组中，分级和风险评估与预测无病生存率和总生存率无关。这些参数的预后相关性与 L1CAM 阳性密切相关。分类和回归决策树（CRT）确定 L1CAM 是预测复发（敏感性=0.74；特异性=0.91）和死亡（敏感性=0.77；特异性=0.89）的最佳变量。
据我们所知，L1CAM 是 FIGO I 期、I 型子宫内膜癌中迄今为止发表的最佳预后因素，明显优于标准的多因素风险评分。I 型癌症中 L1CAM 的表达表明需要辅助治疗。这种黏附分子可能作为目前正在开发用于临床应用的完全人源化抗 L1CAM 抗体的治疗靶点。
