Ross A A, Cooper B W, Lazarus H M, Mackay W, Moss T J, Ciobanu N, Tallman M S, Kennedy M J, Davidson N E, Sweet D
BIS Laboratories, Reseda, CA 91335.
Blood. 1993 Nov 1;82(9):2605-10.
Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.
尽管外周血干细胞采集物(PBSC)被认为比骨髓(BM)的肿瘤累及更少,但乳腺癌患者循环肿瘤细胞的发生率尚未得到广泛研究。我们前瞻性地调查了接受大剂量化疗/造血干细胞移植的乳腺癌患者的PBSC和BM采集中肿瘤细胞累及的发生率和活力。使用免疫细胞化学技术分析了48例患者的配对PBSC和BM样本,该技术可检测每5×10⁵个单核细胞中的一个上皮来源肿瘤细胞。在9/48(18.7%)患者的9.8%(13/133)PBSC样本中检测到免疫染色的肿瘤细胞,在32/48(66.7%)患者的62.3%(38/61)BM样本中检测到肿瘤细胞,这一比例显著高于PBSC(P<.005)。污染的PBSC样本中肿瘤细胞的几何平均浓度为0.8/10⁵个单核细胞(范围为0.33至2.0/10⁵),而BM中的为22.9/10⁵个单核细胞(范围为1至3,000/10⁵,P<.0001)。在培养实验中,26个免疫细胞化学阳性样本中有21个形成了克隆性肿瘤集落。在32个免疫细胞化学阴性样本中的30个未检测到肿瘤集落生长。BM和PBSC中肿瘤累及的免疫细胞化学检测与体外克隆生长显著相关(P<.0001)。我们得出结论,晚期乳腺癌患者的PBSC中肿瘤细胞比配对的BM样本少,并且这些肿瘤细胞似乎能够在体外进行克隆生长。