Molecular detection of occult cancer cells in human lung cancer

肿瘤细胞从原发部位脱离并释放到循环中是转移级联的早期事件之一。尽管循环肿瘤细胞的存在并不一定与随后全身性疾病的出现相关，但一些此类肿瘤细胞可能具有建立转移的潜力，因此可能对患者预后产生负面影响。由于循环细胞的数量可能非常少，它们的检测方法需要既灵敏又特异性。形态学、流式细胞术、常规细胞遗传学和免疫细胞化学已被用于检测循环肿瘤细胞。然而，这些技术相对不敏感，依赖于抗体与肿瘤相关细胞表面抗原的相互作用。如果抗体与正常抗原发生交叉反应，或者肿瘤抗原出现在宿主免疫细胞上，这些方法可能产生假阳性结果。包括聚合酶链反应（PCR）的出现在内的分子技术的最新发展使得对外周血循环肿瘤细胞的敏感检测成为可能。一些研究人员使用癌胚抗原（CEA）作为靶基因，因为CEA mRNA可以在包括癌细胞在内的几乎所有上皮细胞中检测到，但不能在非上皮细胞中检测到。CEA mRNA逆转录聚合酶链反应（RT-PCR）扩增法是检测外周血循环癌细胞的有效手段。如果在血液样本中检测到CEA mRNA，这意味着异位上皮细胞的存在，因此可能是癌细胞。术前血液样本中CEA mRNA阳性的患者与CEA mRNA阴性的患者相比，生存率较低；在这些患者中，术后血液样本中CEA mRNA阳性的患者生存率最差。术前外周血CEA mRNA的分子检测是肺癌根治性手术患者预后的一个独立因素。少

The detachment of tumor cells from the primary site and the release of them into the circulation is one of the early events in the metastatic cascade. Although the presence of circulating tumor cells does not necessarily correlate with the subsequent appearance of systemic disease, some such tumor cells may have the potential to establish metastases and so may have a negative influence on patient prognosis. Since the number of circulating cells may be very small, methods for their detection need to be both sensitive and specific. Morphology, flow cytometry, conventional cytogenetics, and immunocytochemistry have been used to detect circulating tumor cells. However, these techniques are relatively insensitive and dependent upon the interaction of antibodies with tumor-associated cell-surface antigens. These methods may yield false-positive results if the antibodies cross-react with normal antigens or if the tumor antigens are presented on host immune cells. Recent developments in molecu … More lar technology including the advent of the polymerase chain reaction (PCR) have permitted the sensitive detection of circulating tumor cells in the peripheral blood. Several researchers have used carcinoembryonic antigen (CEA) as the target gene because CEA mRNA can be detected in almost all epithelial cells, including cancer cells, but not in non-epithelial cells. The reverse transcriptase-polymerase chain reaction (RT-PCR) amplification method for CEA mRNA is an efficient means of detecting circulating cancer cells in the peripheral blood. If CEA mRNA is detected in blood samples, this implies the presence of ectopic epithelial cells, and hence presumably cancer cells. Patients with positive CEA mRNA in the preoperative blood samples had a poor survival when compared to those with negative CEA mRNA ; of these patients, the worst survival rate was seen in those with positive CEA mRNA in the postoperative blood samples. The molecular detection of CEA mRNA in the preoperative peripheral blood is an independent prognostic factor in patients with lung cancer who undergo a curative surgery. Less