Mezzanzanica Delia, Fabbi Marina, Bagnoli Marina, Staurengo Samantha, Losa Marco, Balladore Emanuela, Alberti Paola, Lusa Lara, Ditto Antonino, Ferrini Silvano, Pierotti Marco A, Barbareschi Mattia, Pilotti Silvana, Canevari Silvana
Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Clin Cancer Res. 2008 Mar 15;14(6):1726-33. doi: 10.1158/1078-0432.CCR-07-0428.
Currently available clinicopathologic prognostic factors are imperfect predictors of clinical course in advanced-stage epithelial ovarian cancer patients. New molecular predictors are needed to identify patients with higher risk of relapse or death from disease. In a retrospective study, we investigated the prognostic impact of activated leukocyte cell adhesion molecule (ALCAM) expression in epithelial ovarian cancer.
We analyzed the effect of cell-anchorage loss on ALCAM cellular localization in vitro and assessed ALCAM expression by immunohistochemistry in a series of 109 well-characterized epithelial ovarian cancer patient samples. Chi-square test, Kaplan-Meier method, and Cox proportional hazard analyses were used to relate ALCAM cellular localization to clinical-pathologic parameters and to overall survival (OS) rate.
Loss of epithelial ovarian cancer cell anchorage was associated both in vitro and in vivo with decreased ALCAM membrane expression. In vivo, ALCAM was localized to cell membrane in normal surface ovarian epithelium, whereas in 67% of the epithelial ovarian cancer samples, membrane localization was decreased or even lost, and the molecule was mainly expressed in cytoplasm. Median OS in this group of patients was 58 months, whereas a median OS was not yet reached in patients with ALCAM membrane localization (P = 0.036, hazard ratio [HR] = 2.0, 95% confidence interval [CI] 1.1 to 3.5). In a multivariate Cox regression model including all the available clinicopathologic variables, loss of ALCAM membrane expression was an independent factor of unfavorable prognosis (P = 0.042, HR = 2.15, 95% CI: 1.0 to 4.5).
Decreased/lost ALCAM membrane expression is a marker of poorer outcome in epithelial ovarian cancer patients and might help to identify patients who could benefit from more frequent follow-up or alternative therapeutic modalities.
目前可用的临床病理预后因素并不能完美预测晚期上皮性卵巢癌患者的临床病程。需要新的分子预测指标来识别疾病复发或死亡风险较高的患者。在一项回顾性研究中，我们调查了活化白细胞细胞黏附分子（ALCAM）表达在上皮性卵巢癌中的预后影响。
我们在体外分析了细胞锚定丧失对ALCAM细胞定位的影响，并通过免疫组织化学评估了109例特征明确的上皮性卵巢癌患者样本中ALCAM的表达。采用卡方检验、Kaplan-Meier法和Cox比例风险分析来关联ALCAM细胞定位与临床病理参数及总生存率（OS）。
上皮性卵巢癌细胞锚定丧失在体外和体内均与ALCAM膜表达降低相关。在体内，ALCAM定位于正常卵巢表面上皮的细胞膜，而在67%的上皮性卵巢癌样本中，膜定位降低甚至丧失，该分子主要表达于细胞质中。这组患者的中位OS为58个月，而ALCAM膜定位患者的中位OS尚未达到（P = 0.036，风险比[HR] = 2.0，95%置信区间[CI] 1.1至3.5）。在包含所有可用临床病理变量的多变量Cox回归模型中，ALCAM膜表达丧失是不良预后的独立因素（P = 0.042，HR = 2.15，95% CI：1.0至4.5）。
ALCAM膜表达降低/丧失是上皮性卵巢癌患者预后较差的标志物，可能有助于识别可从更频繁随访或替代治疗模式中获益的患者。
