Mazumdar Madhu, Bacik Jennifer, Tickoo Satish K, Dobrzynski Deborah, Donadio Alessia, Bajorin Dean, Motzer Robert, Reuter Victor, Bosl George J
Memorial Sloan-Kettering Cancer Center, 307 E 63rd St, 3rd Floor, New York, NY 10021, USA.
J Clin Oncol. 2003 Jul 15;21(14):2679-88. doi: 10.1200/JCO.2003.03.136.
The prognostic information provided by alpha-fetoprotein and human chorionic gonadotrophin in the management of germ cell tumor (GCT) patients is a biochemical reflection of tumor differentiation. Ki67, p53, and apoptosis have been found to be related to proliferation (Ki67), cell death (p53, apoptosis), and possibly differentiation chemoresistance (p53). We sought to determine whether simultaneous expression of one or more of these markers could identify clinically relevant subgroups of patients with nonseminomatous GCT (NSGCT).
These five marker values were obtained for 95 previously untreated patients with embryonal carcinoma with or without other germ cell components. A multivariate cluster analysis was performed to identify patients with similar marker patterns.
One prominent cluster (n = 37; 36 testis retroperitoneum), consisting of 26 (70%) good-risk (GR), nine (24%) intermediate-risk (IR), and two (6%) poor-risk (PR) patients, as defined by the International Germ Cell Consensus Cancer Group (IGCCCG), was observed. The 5-year survival of the prominent cluster (with 30% IR/PR patients) was 94% (95% confidence interval [CI], 86% to 100%), which is comparable to the 91% (95% CI, 89% to 93%) 5-year survival of the IGCCCG GR patients. IGCCCG risk status (P =.005) and cluster affiliation (P =.04) were independent predictors of outcome with hazard ratios of 5.0 (95% CI, 1.6 to 15.4) and 4.6 (95% CI, 1.04 to 20.1), respectively.
These results suggest that there is a subgroup of NSGCT patients with embryonal carcinoma (with or without other histologies) with a specific tumor biology profile (high Ki67, low apoptosis, and low p53) whose survival is better than that of the overall patient group. The unexpectedly good outcome for the prominent cluster and independent-risk status suggest that subgroups of GCT reflecting different abilities to respond to treatment exist within IGCCCG prognostic categories.
甲胎蛋白和人绒毛膜促性腺激素在生殖细胞肿瘤（GCT）患者管理中提供的预后信息是肿瘤分化的生化反映。已发现Ki67、p53和细胞凋亡与增殖（Ki67）、细胞死亡（p53、细胞凋亡）以及可能的分化化疗耐药性（p53）相关。我们试图确定这些标志物中一种或多种的同时表达是否能识别非精原细胞瘤性GCT（NSGCT）患者的临床相关亚组。
获取了95例先前未经治疗的伴有或不伴有其他生殖细胞成分的胚胎癌患者的这五个标志物值。进行多变量聚类分析以识别具有相似标志物模式的患者。
观察到一个显著聚类（n = 37；36例睾丸腹膜后），由26例（70%）低风险（GR）、9例（24%）中风险（IR）和2例（6%）高风险（PR）患者组成，这是根据国际生殖细胞共识癌症小组（IGCCCG）定义的。该显著聚类（含30%的IR/PR患者）的5年生存率为94%（95%置信区间[CI]，86%至100%），与IGCCCG GR患者91%（95% CI，89%至93%）的5年生存率相当。IGCCCG风险状态（P = 0.005）和聚类归属（P = 0.04）是结局的独立预测因素，风险比分别为5.0（95% CI，1.6至15.4）和4.6（95% CI，1.04至20.1）。
这些结果表明，存在一组NSGCT患者，其患有胚胎癌（伴有或不伴有其他组织学类型），具有特定的肿瘤生物学特征（高Ki67、低细胞凋亡和低p53），其生存率优于总体患者组。该显著聚类出人意料的良好结局以及独立风险状态表明，在IGCCCG预后类别中存在反映不同治疗反应能力的GCT亚组。
