Paterlini-Brechot Patrizia, Benali Naoual Linda
INSERM, Unité 807, Paris, F-75730 France.
Cancer Lett. 2007 Aug 18;253(2):180-204. doi: 10.1016/j.canlet.2006.12.014. Epub 2007 Feb 20.
Recent molecular and clinical studies have shown that invasion may occur very early in tumor development, thus emphasizing the potential importance of specific and sensitive detection of circulating tumor cells (CTC) and circulating tumor microemboli (CTM). The technical challenge in this field consists of finding "rare" tumor cells (just a few CTCs mixed with the approximately 10 million leukocytes and 5 billion erythrocytes in 1ml of blood) and being able to distinguish them from epithelial non-tumor cells and leukocytes. Many recent studies have discussed the clinical impact of detecting CTC/CTM. Although conflicting results have been obtained, these studies suggest the vast potential of CTC/CTM detection in cancer prognosis and follow up. However, the variable technical approaches which were used, as well as the number of millilitres of blood analyzed, the quality of sensitivity and specificity tests, the number of patients versus controls and the data interpretation make it very difficult to draw firm conclusions. A particularly important recent finding is that invasive tumor cells tend to loose their epithelial antigens by the epithelial to mesenchymal transition (EMT) process. Furthermore, it is known that non-tumor epithelial cells can also be present in blood. Thus, it appears that a reliable diagnostic identification of CTC and CTM cannot be based on the expression of epithelial-specific transcripts or antigens. Cytopathological examination of CTC/CTM, sensitively enriched from blood, represents a potentially useful alternative and can now be employed in routine analyses as a specific diagnostic assay, and be tested in large, blind, multicenter clinical trials. This basic approach can be complemented by immunological and molecular studies for further characterization of CTC/CTM and of their malignant potential. This review is aimed at helping oncologists critically evaluate past and future research work in this field. The interest in development and assessment of this noninvasive marker should lead to more effective and better tailored anticancer treatments for individual patients, thus resulting in their improved life expectancy.
近期的分子和临床研究表明，肿瘤侵袭可能在肿瘤发展的极早期就已发生，这凸显了特异性且灵敏地检测循环肿瘤细胞（CTC）和循环肿瘤微栓子（CTM）的潜在重要性。该领域的技术挑战在于找到“罕见”的肿瘤细胞（即在1毫升血液中，仅有少数CTC混杂在约1000万个白细胞和50亿个红细胞之中），并能够将它们与上皮非肿瘤细胞及白细胞区分开来。近期的许多研究探讨了检测CTC/CTM的临床意义。尽管研究结果存在冲突，但这些研究表明，CTC/CTM检测在癌症预后和随访方面具有巨大潜力。然而，所采用的技术方法各异，分析的血液毫升数、敏感性和特异性测试的质量、患者与对照的数量以及数据解读等因素，使得很难得出确凿的结论。近期一项尤为重要的发现是，侵袭性肿瘤细胞往往通过上皮-间质转化（EMT）过程丧失其上皮抗原。此外，已知非肿瘤上皮细胞也可存在于血液中。因此，似乎不能基于上皮特异性转录本或抗原的表达来可靠地诊断识别CTC和CTM。对从血液中灵敏富集的CTC/CTM进行细胞病理学检查，是一种潜在有用的替代方法，目前可作为一种特异性诊断检测方法用于常规分析，并在大规模、盲法、多中心临床试验中进行检验。这种基本方法可通过免疫学和分子研究加以补充，以进一步表征CTC/CTM及其恶性潜能。本综述旨在帮助肿瘤学家批判性地评估该领域过去和未来的研究工作。对这种非侵入性标志物的开发和评估的关注，应能为个体患者带来更有效、更具针对性的抗癌治疗，从而提高他们的预期寿命。
