多药耐药基因（MDR-1）与上皮性卵巢癌、输卵管癌和腹膜癌脑转移风险。
Multidrug resistance gene (MDR-1) and risk of brain metastasis in epithelial ovarian, fallopian tube, and peritoneal cancer.
机构信息
Department of Gynecologic Oncology, MD-Anderson Cancer Center, University of Texas, Houston, 77230-1439, USA.
出版信息
Am J Clin Oncol. 2011 Oct;34(5):488-93. doi: 10.1097/COC.0b013e3181ec5f4b.
BACKGROUND
To evaluate risk factors that predict brain metastasis in epithelial ovarian, fallopian tube, and peritoneal cancer.
METHODS
All patients with FIGO stage I to IV who underwent initial cytoreductive surgery between January 1995 and January 2009 were evaluated. The tumor samples were evaluated for 7 markers including multidrug resistance gene (MDR-1), DNA aneuploidity and S-phase fraction, human epidermal growth factor receptor 2, estrogen receptor, progesterone receptor, p53 mutation, epidermal growth factor receptor, and CD31. Biomarker expression was evaluated as a predictor of hematogenous metastasis to the following locations: (i) liver and spleen, (ii) lung, and (iii) brain.
RESULTS
There were 309 cases identified during the period. Of those, 5 (1.6%, 95% CI: 0.2%-3.0%) women developed brain metastasis. Time to onset of brain metastasis was significantly longer than that for other recurrent sites (median time to recurrence after initial cytoreduction, brain vs. lung vs. liver, 21.4 vs. 12.6 vs. 11.0 months, P< 0.05). Significantly increased expression of MDR-1 was seen in tumors from women who developed brain metastasis (brain vs. nonbrain sites, 80% vs. 4.2%-24.3%, P= 0.004). In multivariate analysis, MDR-1 was the only significant variable associated with the risk of brain metastasis. MDR-1 expression predicted brain metastasis (receiver-operator-characteristic curve analysis, AUC 0.808, P= 0.018), and with a 10% positive expression of MDR-1 as the cutoff value, sensitivity, specificity, positive predictive value, negative predictive value, accuracy of prediction of brain metastasis were 80%, 86.1%, 15.4%, 99.3%, and 85.9%, respectively (odds ratio: 24.7, 95% CI: 2.64-232, P= 0.002).
CONCLUSIONS
Increased expression of MDR-1 in the tumor tissue obtained at initial cytoreduction is associated with increased risk of developing brain metastases in women with epithelial ovarian, fallopian tube, or peritoneal cancer.
背景
评估上皮性卵巢癌、输卵管癌和腹膜癌发生脑转移的预测因素。
方法
评估了 1995 年 1 月至 2009 年 1 月期间接受初始细胞减灭术的所有国际妇产科联盟（FIGO）分期 I 至 IV 期的患者。评估了肿瘤样本中的 7 种标志物，包括多药耐药基因（MDR-1）、DNA 非整倍体和 S 期分数、人表皮生长因子受体 2、雌激素受体、孕激素受体、p53 突变、表皮生长因子受体和 CD31。生物标志物表达被评估为血液转移到以下部位的预测因子：（i）肝和脾，（ii）肺，和（iii）脑。
结果
在该期间确定了 309 例病例。其中，5 例（1.6%，95%CI：0.2%-3.0%）女性发生脑转移。脑转移的发病时间明显长于其他复发部位（初次细胞减灭后复发的中位时间，脑与肺与肝，21.4 与 12.6 与 11.0 个月，P<0.05）。在发生脑转移的女性的肿瘤中，MDR-1 的表达显著增加（脑与非脑部位，80%与 4.2%-24.3%，P=0.004）。多变量分析显示，MDR-1 是唯一与脑转移风险相关的显著变量。MDR-1 表达预测脑转移（接受者操作特征曲线分析，AUC 0.808，P=0.018），以 MDR-1 阳性表达 10%为截断值，脑转移的灵敏度、特异性、阳性预测值、阴性预测值和预测准确性分别为 80%、86.1%、15.4%、99.3%和 85.9%（优势比：24.7，95%CI：2.64-232，P=0.002）。
结论
在初次细胞减灭术时获得的肿瘤组织中 MDR-1 的表达增加与上皮性卵巢癌、输卵管癌或腹膜癌女性发生脑转移的风险增加相关。
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