Fizazi K, Morat L, Chauveinc L, Prapotnich D, De Crevoisier R, Escudier B, Cathelineau X, Rozet F, Vallancien G, Sabatier L, Soria J C
Department of Medicine, Institut Gustave Roussy, Villejuif, France.
Ann Oncol. 2007 Mar;18(3):518-21. doi: 10.1093/annonc/mdl419.
Circulating tumor cells (CTCs) cannot be readily detected with currently available methods in the majority of patients with prostate cancer. Telomerase activation, one of the major immortalization events, is found in most cases of prostate cancer. We attempted to develop a method using telomerase activity to isolate CTCs in patients with prostate cancer.
Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood using Ficoll-Hypaque. Immunomagnetic beads coated with an epithelial cell-specific antigen antibody (BerEP4) were used to harvest epithelial cells from PBMCs. Telomerase activity was detected in harvested epithelial cells using the telomerase-PCR-enzyme-linked immunosorbent assay method.
Blood samples from 107 patients with prostate cancer were studied. CTCs were detected in 19 of 24 (79%) patients with advanced prostate cancer. In contrast, CTCs were not detected in blood samples from 22 healthy male volunteers. CTCs were even identified in patients with an undetectable (<0.1 ng/ml) serum prostate-specific antigen (PSA). CTCs were detected in 55 of 70 (79%) patients with localized prostate cancer before radical prostatectomy (n = 30) or brachytherapy (n = 40). CTCs were also detected in 3 of 13 patients (23%) with an undetectable serum PSA measured at least 1 year after radical prostatectomy, which is consistent with the expected relapse rate in this setting.
CTCs can be detected using telomerase activity in a large majority and a wide variety of patients with prostate cancer, including those with localized disease.
在大多数前列腺癌患者中，目前可用的方法难以轻易检测到循环肿瘤细胞（CTC）。端粒酶激活是主要的永生化事件之一，在大多数前列腺癌病例中均可发现。我们试图开发一种利用端粒酶活性来分离前列腺癌患者循环肿瘤细胞的方法。
使用Ficoll-Hypaque从全血中分离外周血单个核细胞（PBMC）。用包被上皮细胞特异性抗原抗体（BerEP4）的免疫磁珠从PBMC中收获上皮细胞。采用端粒酶-PCR-酶联免疫吸附测定法检测收获的上皮细胞中的端粒酶活性。
对107例前列腺癌患者的血样进行了研究。在24例晚期前列腺癌患者中的19例（79%）检测到了循环肿瘤细胞。相比之下，22名健康男性志愿者的血样中未检测到循环肿瘤细胞。在血清前列腺特异性抗原（PSA）检测不到（<0.1 ng/ml）的患者中也发现了循环肿瘤细胞。在70例局限性前列腺癌患者中，55例（79%）在根治性前列腺切除术（n = 30）或近距离放射治疗（n = 40）前检测到了循环肿瘤细胞。在根治性前列腺切除术后至少1年血清PSA检测不到的13例患者中的3例（23%）也检测到了循环肿瘤细胞，这与该情况下预期的复发率一致。
在绝大多数以及包括局限性疾病患者在内的广泛前列腺癌患者中，可利用端粒酶活性检测循环肿瘤细胞。
