Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA.
Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA; Vitatex Inc., 25 Health Sciences Drive, Stony Brook, NY 11790, USA.
Gynecol Oncol. 2014 Sep;134(3):581-90. doi: 10.1016/j.ygyno.2014.06.013. Epub 2014 Jun 24.
Circulating tumor cells (CTCs) have been introduced as a biomarker in detecting advanced epithelial ovarian cancer (EOC). The goals are to examine the prevalence of the invasive subpopulation of CTCs (iCTCs) in patients at high risk of EOC and to compare this biomarker to serum CA125.
We used a unique cell adhesion matrix (CAM)-based, functional cell enrichment and identification platform to isolate iCTCs from 129 preoperative patients. We confirmed the identity of iCTCs using positive epithelial (Epi+) markers and negative hematopoietic lineage (HL-) markers. Sensitivity and specificity of the assays were examined and iCTCs/CA125 were correlated with overall survival (OS), progression-free survival (PFS) and clinical parameters.
We found a 41.2% sensitivity, 95.1% specificity and 77.8% positive predictive value (PPV) of the iCTC assay in detecting patients with stage I and II EOC malignancy, and a 83% sensitivity and 97.3% PPV in detecting all stages of EOC malignancy. However, a positive CA125 test provided weak evidence to detect stage I and II malignancy (61.6% PPV) and all EOC (92.1% PPV), because of its 76.2% specificity. A significantly stronger concordance in OS and PFS of clinical factors (tumor stage, debulking and platinum sensitivity) was noted for elevated iCTCs than for serum CA125.
The CAM-initiated CTC enrichment/identification method enabled the detection of early stage EOC. iCTCs were better correlated with worse OS and PFS, more specific and better PPV than CA125 in detecting EOC malignancy in patients at high risk of EOC.
循环肿瘤细胞（CTCs）已被引入作为检测晚期上皮性卵巢癌（EOC）的生物标志物。目的是检查高危 EOC 患者中侵袭性 CTC 亚群（iCTCs）的流行情况，并将该生物标志物与血清 CA125 进行比较。
我们使用独特的基于细胞黏附基质（CAM）的功能细胞富集和鉴定平台，从 129 名术前患者中分离 iCTCs。我们使用阳性上皮（Epi+）标志物和阴性造血谱系（HL-）标志物来确认 iCTCs 的身份。检查了测定的敏感性和特异性，并将 iCTCs/CA125 与总生存期（OS）、无进展生存期（PFS）和临床参数相关联。
我们发现 iCTC 检测 I 期和 II 期 EOC 恶性肿瘤患者的敏感性为 41.2%，特异性为 95.1%，阳性预测值（PPV）为 77.8%，检测所有阶段 EOC 恶性肿瘤的敏感性为 83%，PPV 为 97.3%。然而，由于其特异性为 76.2%，CA125 检测呈阳性提供了检测 I 期和 II 期恶性肿瘤（PPV 为 61.6%）和所有 EOC（PPV 为 92.1%）的弱证据。与血清 CA125 相比，升高的 iCTCs 与 OS 和 PFS 的临床因素（肿瘤分期、减瘤术和铂类敏感性）的一致性更强。
CAM 启动的 CTC 富集/鉴定方法能够检测早期 EOC。与 CA125 相比，iCTCs 在检测高危 EOC 患者的 EOC 恶性肿瘤中与更差的 OS 和 PFS 更相关，更特异，PPV 更好。
