Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver, BC, Canada.
N Engl J Med. 2010 Mar 11;362(10):875-85. doi: 10.1056/NEJMoa0905680.
Despite advances in treatments for Hodgkin's lymphoma, about 20% of patients still die from progressive disease. Current prognostic models predict the outcome of treatment with imperfect accuracy, and clinically relevant biomarkers have not been established to improve on the International Prognostic Score.
Using gene-expression profiling, we analyzed 130 frozen samples obtained from patients with classic Hodgkin's lymphoma during diagnostic lymph-node biopsy to determine which cellular signatures were correlated with treatment outcome. We confirmed our findings in an independent cohort of 166 patients, using immunohistochemical analysis.
Gene-expression profiling identified a gene signature of tumor-associated macrophages that was significantly associated with primary treatment failure (P=0.02). In an independent cohort of patients, we found that an increased number of CD68+ macrophages was correlated with a shortened progression-free survival (P=0.03) and with an increased likelihood of relapse after autologous hematopoietic stem-cell transplantation (P=0.008), resulting in shortened disease-specific survival (P=0.003). In multivariate analysis, this adverse prognostic factor outperformed the International Prognostic Score for disease-specific survival (P=0.003 vs. P=0.03). The absence of an elevated number of CD68+ cells in patients with limited-stage disease defined a subgroup of patients with a long-term disease-specific survival of 100% with the use of current treatment strategies.
An increased number of tumor-associated macrophages was strongly associated with shortened survival in patients with classic Hodgkin's lymphoma and provides a new biomarker for risk stratification.
尽管霍奇金淋巴瘤的治疗方法取得了进展，但仍有约 20%的患者死于疾病进展。目前的预后模型预测治疗结果的准确性并不完美，也没有建立与国际预后评分相关的临床相关生物标志物来改善预后。
我们使用基因表达谱分析了 130 例经典霍奇金淋巴瘤患者在诊断性淋巴结活检时获得的冷冻样本，以确定哪些细胞特征与治疗结果相关。我们使用免疫组织化学分析在 166 例独立患者的队列中验证了我们的发现。
基因表达谱分析确定了一个与肿瘤相关巨噬细胞的基因特征，该特征与原发性治疗失败显著相关（P=0.02）。在一个独立的患者队列中，我们发现 CD68+巨噬细胞数量的增加与无进展生存期缩短相关（P=0.03），与自体造血干细胞移植后复发的可能性增加相关（P=0.008），从而导致疾病特异性生存期缩短（P=0.003）。在多变量分析中，这个不利的预后因素在疾病特异性生存方面优于国际预后评分（P=0.003 与 P=0.03）。在局限性疾病患者中，如果没有发现 CD68+细胞数量升高，则定义了一个亚组患者，他们在使用当前治疗策略时，疾病特异性生存期达到 100%。
肿瘤相关巨噬细胞数量的增加与经典霍奇金淋巴瘤患者的生存时间缩短密切相关，并为风险分层提供了一个新的生物标志物。
