Concurrent Expression of MYC and BCL2 in Diffuse Large B-Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone
Concurrent Expression of MYC and BCL2 in Diffuse Large B-Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone
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DOI：
10.1200/jco.2011.41.0985
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发表时间：
2012-10-01
影响因子：
45.3
通讯作者：
Gascoyne, Randy D.
中科院分区：
文献类型：
--
作者：
Johnson, Nathalie A.;Slack, Graham W.;Gascoyne, Randy D.
弥漫性大B细胞淋巴瘤（DLBCL）经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）治疗后，60%的患者可治愈。MYC易位，伴或不伴BCL 2易位，与DLBCL的低生存率相关。我们研究了MYC蛋白的表达，有或没有BCL 2蛋白的表达，是否可以在diagnosis.Patients和MethodsWe确定的MYC和BCL 2蛋白的免疫组化（IHC）与生存在两个独立的队列DLBCL患者与R-CHOP治疗的存在之间的相关性。我们进一步确定，如果MYC蛋白表达与高MYC mRNA和/或存在的MYC translocation.ResultsIn的训练队列（n = 167），MYC和BCL 2蛋白分别检测到29%和44%的患者。同时表达（MYC阳性/BCL 2阳性）存在于21%的患者中。MYC蛋白与高MYC mRNA和MYC易位的存在相关（均P <0.001），但后者较不常见（均为11%）。MYC蛋白表达仅与BCL 2蛋白共表达时总体生存率和无进展生存率较低相关（P <0.001）。重要的是，MYC阳性/BCL 2阳性的不良预后影响在140例DLBCL患者的独立队列中得到验证，并且仍然显著（P <0.05）在多变量模型中调整高危特征后，包括升高的国际预后指数评分，活化的B细胞分子亚型，和存在的并发MYC和BCL 2 translocation.ConclusionAssessment的MYC和BCL 2表达的IHC代表了一个强大的，快速的，廉价的方法，在诊断DLBCL患者的风险分层。J Clin Oncol 30：3452-3459. (C)2012年美国临床肿瘤学会
PurposeDiffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations, have been associated with inferior survival in DLBCL. We investigated whether expression of MYC protein, with or without BCL2 protein expression, could risk-stratify patients at diagnosis.Patients and MethodsWe determined the correlation between presence of MYC and BCL2 proteins by immunohistochemistry (IHC) with survival in two independent cohorts of patients with DLBCL treated with R-CHOP. We further determined if MYC protein expression correlated with high MYC mRNA and/or presence of MYC translocation.ResultsIn the training cohort (n = 167), MYC and BCL2 proteins were detected in 29% and 44% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. MYC protein correlated with presence of high MYC mRNA and MYC translocation (both P < .001), but the latter was less frequent (both 11%). MYC protein expression was only associated with inferior overall and progression-free survival when BCL2 protein was coexpressed (P < .001). Importantly, the poor prognostic effect of MYC positive/BCL2 positive was validated in an independent cohort of 140 patients with DLBCL and remained significant (P < .05) after adjusting for presence of high-risk features in a multivariable model that included elevated international prognostic index score, activated B-cell molecular subtype, and presence of concurrent MYC and BCL2 translocations.ConclusionAssessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis. J Clin Oncol 30:3452-3459. (C) 2012 by American Society of Clinical Oncology