O'Shea Derville, O'Riain Ciarán, Taylor Claire, Waters Rachel, Carlotti Emanuela, Macdougall Finlay, Gribben John, Rosenwald Andreas, Ott German, Rimsza Lisa M, Smeland Erlend B, Johnson Nathalie, Campo Elias, Greiner Timothy C, Chan Wing C, Gascoyne Randy D, Wright George, Staudt Louis M, Lister T Andrew, Fitzgibbon Jude
Centre for Medical Oncology, Barts and the London School of Medicine, London, United Kingdom.
Blood. 2008 Oct 15;112(8):3126-9. doi: 10.1182/blood-2008-05-154013. Epub 2008 Jul 15.
The International Prognostic Index and the Follicular Lymphoma International Prognostic Index are widely used for the risk assessment of follicular lymphoma (FL). Although molecular studies have provided insight into the biology of FL, no molecular marker has impacted on treatment stratification. Because TP53 mutations are associated with poor prognosis in hematologic malignancies, we investigated the prognostic value of TP53 mutation at diagnosis in FL. Heterozygous TP53 mutation was detected in 12 of 185 (6%) analyzed cases. Mutation was associated with older age (P = .02) and higher International Prognostic Index score (P = .04). On multivariate analysis, TP53 mutation correlated with shorter progression-free survival (P < .001) and overall survival (P = .009). TP53 mutation was associated with low expression of the immune-response 1 gene expression signature (P = .016) and with an unfavorable gene expression-based survival predictor score (P < .001), demonstrating for the first time that molecular features of the malignant cell may correlate with the nature of the immune response in FL.
国际预后指数(International Prognostic Index)和滤泡性淋巴瘤国际预后指数(Follicular Lymphoma International Prognostic Index)被广泛用于滤泡性淋巴瘤(FL)的风险评估。尽管分子研究已深入了解FL的生物学特性,但尚无分子标志物影响治疗分层。由于TP53突变与血液系统恶性肿瘤的不良预后相关,我们研究了FL诊断时TP53突变的预后价值。在185例分析病例中的12例(6%)检测到杂合性TP53突变。突变与年龄较大(P = .02)和较高的国际预后指数评分(P = .04)相关。多因素分析显示,TP53突变与无进展生存期较短(P < .001)和总生存期较短(P = .009)相关。TP53突变与免疫反应1基因表达特征的低表达相关(P = .016),并与基于基因表达的不良生存预测评分相关(P < .001),首次证明恶性细胞的分子特征可能与FL中免疫反应的性质相关。