Natkunam Yasodha, Farinha Pedro, Hsi Eric D, Hans Christine P, Tibshirani Robert, Sehn Laurie H, Connors Joseph M, Gratzinger Dita, Rosado Manuel, Zhao Shuchun, Pohlman Brad, Wongchaowart Nicholas, Bast Martin, Avigdor Abraham, Schiby Ginette, Nagler Arnon, Byrne Gerald E, Levy Ronald, Gascoyne Randy D, Lossos Izidore S
Department of Pathology, Division of Oncology, Stanford University School of Medicine, Stanford, CA, USA.
J Clin Oncol. 2008 Jan 20;26(3):447-54. doi: 10.1200/JCO.2007.13.0690. Epub 2007 Dec 17.
The heterogeneity of diffuse large B-cell lymphoma (DLBCL) has prompted the search for new markers that can accurately separate prognostic risk groups. We previously showed in a multivariate model that LMO2 mRNA was a strong predictor of superior outcome in DLBCL patients. Here, we tested the prognostic impact of LMO2 protein expression in DLBCL patients treated with anthracycline-based chemotherapy with or without rituximab.
DLBCL patients treated with anthracycline-based chemotherapy alone (263 patients) or with the addition of rituximab (80 patients) were studied using immunohistochemistry for LMO2 on tissue microarrays of original biopsies. Staining results were correlated with outcome.
In anthracycline-treated patients, LMO2 protein expression was significantly correlated with improved overall survival (OS) and progression-free survival (PFS) in univariate analyses (OS, P = .018; PFS, P = .010) and was a significant predictor independent of the clinical International Prognostic Index (IPI) in multivariate analysis. Similarly, in patients treated with the combination of anthracycline-containing regimens and rituximab, LMO2 protein expression was also significantly correlated with improved OS and PFS (OS, P = .005; PFS, P = .009) and was a significant predictor independent of the IPI in multivariate analysis.
We conclude that LMO2 protein expression is a prognostic marker in DLBCL patients treated with anthracycline-based regimens alone or in combination with rituximab. After further validation, immunohistologic analysis of LMO2 protein expression may become a practical assay for newly diagnosed DLBCL patients to optimize their clinical management.
弥漫性大B细胞淋巴瘤（DLBCL）的异质性促使人们寻找能够准确区分预后风险组的新标志物。我们之前在一个多变量模型中表明，LMO2 mRNA是DLBCL患者预后良好的有力预测指标。在此，我们测试了LMO2蛋白表达对接受含蒽环类化疗（无论是否联合利妥昔单抗）的DLBCL患者的预后影响。
对仅接受含蒽环类化疗的DLBCL患者（263例）或联合利妥昔单抗治疗的患者（80例），使用免疫组织化学方法检测其原发活检组织芯片上的LMO2。染色结果与预后相关。
在接受蒽环类治疗的患者中，单变量分析显示LMO2蛋白表达与总生存期（OS）和无进展生存期（PFS）的改善显著相关（OS，P = 0.018；PFS，P = 0.010），多变量分析表明它是独立于临床国际预后指数（IPI）的显著预测指标。同样，在接受含蒽环类方案联合利妥昔单抗治疗的患者中，LMO2蛋白表达也与OS和PFS的改善显著相关（OS，P = 0.005；PFS，P = 0.009），多变量分析显示它是独立于IPI的显著预测指标。
我们得出结论，LMO2蛋白表达是接受单独含蒽环类方案或联合利妥昔单抗治疗的DLBCL患者的预后标志物。经过进一步验证后，LMO2蛋白表达的免疫组织学分析可能会成为新诊断DLBCL患者优化临床管理的实用检测方法。
