Assistance Publique-Hôpitaux de Paris, Groupe Henri Mondor-Albert Chenevier, L'Institut National de la Santé et de la Recherche Médicale, Unité 955, Institut Mondor de Recherche Biomédicale; Université Paris 12, Faculté de médecine, Créteil.
J Clin Oncol. 2009 Nov 20;27(33):5573-9. doi: 10.1200/JCO.2009.22.7058. Epub 2009 Sep 28.
To evaluate the prognostic value of cell of origin immunohistochemical markers and BCL2, BCL6, and c-MYC translocations in a homogeneous cohort of patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).
Patients with CD20+ DLBCL were enrolled in the randomized LNH98-5 and 01-5B Groupe d'Etude des Lymphomes de l'Adulte trials. Paraffin-embedded tumor samples of 119 patients treated with R-CHOP were analyzed by immunohistochemistry for CD10, BCL6, MUM1/IRF4, LMO2, and forkhead box protein P1 (FOXP1) expression and for BCL2, BCL6, and c-MYC breakpoints by fluorescence in situ hybridization (FISH) on tissue microarray.
LMO2 expression and BCL2 breakpoint were associated with the germinal center (GC) subtype defined by Hans' algorithm, respectively (P < .0001; P = .0002) whereas FOXP1 expression and BCL6 breakpoint were associated with the non-germinal center (non-GC) subtype (P = .008 and P = .0001, respectively). The immunohistochemical markers analyzed independently, GC/non-GC phenotype and BCL2 breakpoint did not predict overall survival (OS). BCL6 breakpoint was significantly associated with an unfavorable impact on OS (P = .04). Interestingly, an immunoFISH index, defined by positivity for at least two of three non-GC markers (FOXP1, MUM1/IRF4, BCL6 breakpoint) was significantly associated with a shorter 5-year OS rate (44%; 95% CI, 28 to 60 v 78%; 95% CI, 59 to 89; P = .01) which was independent (P = .04) of the age-adjusted International Prognostic Index (P = .04) in multivariate analysis.
Our study demonstrates that combining immunohistochemistry with FISH allows construction of an immunoFISH index that significantly predicts survival in elderly DLBCL patients treated with R-CHOP.
评估细胞起源免疫组织化学标志物以及 BCL2、BCL6 和 c-MYC 易位在接受利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松（R-CHOP）治疗的弥漫性大 B 细胞淋巴瘤（DLBCL）同质患者队列中的预后价值。
入组了 LNH98-5 和 01-5B Groupe d'Etude des Lymphomes de l'Adulte 试验的 CD20+DLBCL 患者。对 119 例接受 R-CHOP 治疗的患者的石蜡包埋肿瘤样本进行免疫组织化学分析，以检测 CD10、BCL6、MUM1/IRF4、LMO2 和叉头框蛋白 P1（FOXP1）的表达，并通过组织微阵列进行荧光原位杂交（FISH）检测 BCL2、BCL6 和 c-MYC 断点。
LMO2 表达和 BCL2 断点分别与 Hans 算法定义的生发中心（GC）亚型相关（P<0.0001；P=0.0002），而 FOXP1 表达和 BCL6 断点与非生发中心（non-GC）亚型相关（P=0.008 和 P=0.0001）。独立分析的免疫组织化学标志物、GC/non-GC 表型和 BCL2 断点均不能预测总生存（OS）。BCL6 断点与 OS 不良影响显著相关（P=0.04）。有趣的是，免疫 FISH 指数，由至少两种非 GC 标志物（FOXP1、MUM1/IRF4、BCL6 断点）的阳性定义，与较短的 5 年 OS 率显著相关（44%；95%CI，28 至 60 与 78%；95%CI，59 至 89；P=0.01），这在多变量分析中是独立于年龄调整后的国际预后指数（P=0.04）的（P=0.04）。
我们的研究表明，将免疫组化与 FISH 相结合可以构建免疫 FISH 指数，该指数可显著预测接受 R-CHOP 治疗的老年 DLBCL 患者的生存情况。
