Moss T J, Reynolds C P, Sather H N, Romansky S G, Hammond G D, Seeger R C
Children's Cancer Study Group, Pasadena, Calif.
N Engl J Med. 1991 Jan 24;324(4):219-26. doi: 10.1056/NEJM199101243240403.
Morphologic evaluation of bone marrow for neuroblastoma cells is a routine and important component of clinical staging. Specific immunostaining of malignant cells with monoclonal antibodies should be more sensitive, however, and may improve the detection of metastases and provide additional prognostic information.
We looked for tumor cells in bone marrow from 197 patients with newly diagnosed neuroblastoma, using immunoperoxidase staining with monoclonal antibodies (immunocytologic analysis) and examination of smears and specimens obtained by trephine biopsy (conventional analysis).
Routine smears and trephine-biopsy specimens were positive for tumor cells in 46 percent of the patients, whereas 67 percent were positive on immunocytologic analysis (P less than 0.0001). Immunocytologic analysis detected bone marrow metastases in 34 percent of patients considered to have only localized or regional disease (Stage I, II, or III). It also identified tumor cells that were not detected by conventional analysis in patients with widespread disease (Stage IV or IVS). Tumor content, as determined by immunocytologic analysis, predicted clinical outcome in relation to the age of the patient at diagnosis. Patients with Stage II or III disease diagnosed after one year of age who did not have occult marrow metastases did well, whereas those with metastases did poorly (P = 0.006). Patients in whom Stage IV disease was diagnosed before they were one year of age did well if bone marrow metastases were few or absent, but had poor survival if the marrow contained more than 0.02 percent tumor cells (P = 0.03).
Immunocytologic analysis of bone marrow aspirates is more sensitive than conventional analysis in detecting tumor cells and provides prognostic information. The relations among marrow metastases, age at diagnosis, and clinical outcome illustrate the biologic heterogeneity of neuroblastoma.
对骨髓中的神经母细胞瘤细胞进行形态学评估是临床分期的常规且重要组成部分。然而，用单克隆抗体对恶性细胞进行特异性免疫染色应该更敏感，并且可能改善转移灶的检测并提供额外的预后信息。
我们用单克隆抗体免疫过氧化物酶染色（免疫细胞分析）以及检查涂片和环钻活检获得的标本（传统分析），在197例新诊断的神经母细胞瘤患者的骨髓中寻找肿瘤细胞。
常规涂片和环钻活检标本在46%的患者中肿瘤细胞呈阳性，而免疫细胞分析为67%呈阳性（P<0.0001）。免疫细胞分析在34%被认为仅患有局限性或区域性疾病（Ⅰ期、Ⅱ期或Ⅲ期）的患者中检测到骨髓转移。它还在患有广泛疾病（Ⅳ期或ⅣS期）的患者中识别出传统分析未检测到的肿瘤细胞。通过免疫细胞分析确定的肿瘤含量可预测与诊断时患者年龄相关的临床结局。1岁以后诊断为Ⅱ期或Ⅲ期疾病且无隐匿性骨髓转移的患者预后良好，而有转移的患者预后较差（P = 0.006）。在1岁前被诊断为Ⅳ期疾病的患者中，如果骨髓转移很少或没有，则预后良好，但如果骨髓中肿瘤细胞超过0.02%，则生存率较低（P = 0.03）。
骨髓穿刺液的免疫细胞分析在检测肿瘤细胞方面比传统分析更敏感，并提供预后信息。骨髓转移、诊断时年龄和临床结局之间的关系说明了神经母细胞瘤的生物学异质性。
