Jovanovic Maja Perunicic, Mihaljevic Biljana, Jakovic Ljubomir, Martinovic Vesna Cemerikic, Fekete Marija Dencic, Andjelic Bosko, Antic Darko, Bogdanovic Andrija, Boricic Novica, Terzic Tatjana, Jelicic Jelena, Milenkovic Sanja
Department of Pathology, Clinical Center of Serbia, Belgrade, Serbia.
J BUON. 2015 May-Jun;20(3):820-8.
Despite major advances in the treatment of diffuse large B cell lymphoma (DLBCL), approximately one third of the patients progress or die, suggesting the existence of additional oncogenic events. The purpose of this study was to evaluate the prognostic value of the "Hans classifier", and BCL2 and MYC protein expression and gene alterations in DLBCL patients treated with CHOP or R-CHOP chemotherapy over a 5-year period. Furthermore, we tried to correlate these parameters with the International Prognostic Index (IPI).
The immunohistochemical (IHC) expression of CD10, BCL6, MUM1 and BCL2 on paraffin-embedded formalin-fixed tumor samples from 103 centroblastic DLBCLs was analyzed. IHC expression of MYC and fluorescence in situ hybridization (FISH) for MYC and BCL2 gene alterations was performed on 67 samples using the tissue microarray (TMA) method.
The Hans algorithm was not predictive of survival in both therapy groups. No significant difference in BCL2 and MYC alterations or MYC protein expression in relation to complete response (CR), event-free survival (EFS) and overall survival (OS) was observed in our study. High IPI correlated significantly with poor outcome and it was identified as independent prognostic factor for OS and EFS (both p=0.000). The 5-year OS was 61% in the R-CHOP compared to 38% in the CHOP group (p=0.007). Rituximab significantly improved the OS in the BCL2 positive (60 vs 29%, p=0.008), and the BCL6 negative (73 vs 25%, p=0.001) cases.
IPI is an independent prognosticator for DL-BCL patients and the addition of rituximab significantly improved survival. Furthermore, patients with BCL2+ and BCL6-DLBCL benefited from R-CHOP.
尽管弥漫性大B细胞淋巴瘤（DLBCL）的治疗取得了重大进展，但仍有大约三分之一的患者病情进展或死亡，这表明存在其他致癌事件。本研究的目的是评估“汉斯分类器”、BCL2和MYC蛋白表达以及基因改变在接受CHOP或R-CHOP化疗5年的DLBCL患者中的预后价值。此外，我们试图将这些参数与国际预后指数（IPI）相关联。
分析了103例中心母细胞性DLBCL石蜡包埋福尔马林固定肿瘤样本中CD10、BCL6、MUM1和BCL2的免疫组化（IHC）表达。使用组织微阵列（TMA）方法对67个样本进行了MYC的IHC表达以及MYC和BCL2基因改变的荧光原位杂交（FISH）检测。
汉斯算法在两个治疗组中均不能预测生存情况。在我们的研究中，未观察到BCL2和MYC改变或MYC蛋白表达在完全缓解（CR）、无事件生存（EFS）和总生存（OS）方面的显著差异。高IPI与不良预后显著相关，并且被确定为OS和EFS的独立预后因素（两者p = 0.000）。R-CHOP组的5年OS为61%，而CHOP组为38%（p = 0.007）。利妥昔单抗在BCL2阳性（60% vs 29%，p = 0.008）和BCL6阴性（73% vs 25%，p = 0.001）病例中显著改善了OS。
IPI是DL-BCL患者的独立预后指标，添加利妥昔单抗可显著提高生存率。此外，BCL2+和BCL6-DLBCL患者从R-CHOP中获益。
