Yang Haiyan, Yin Wenjuan, Wu Meijuan, Sun Wenyong
Pathology Department, Zhejiang Cancer Hospital, Hangzhou 310022, China.
Zhonghua Xue Ye Xue Za Zhi. 2015 Aug;36(8):656-61. doi: 10.3760/cma.j.issn.0253-2727.2015.08.006.
To investigate the effect of BCL-2/MYC double-hit on prognosis in diffuse large B-cell lymphoma(DLBCL).
A retrospective study was conducted to investigate clinical and pathological data of 111 patients with DLBCL. CD10, BCL-6, MUM-1, BCL-2 protein expressions were examined by immune-histochemical methods, and abnormal BCL-2 and MYC genes were analyzed by FISH for patients with sufficient pathological data. SAS 8.2 was adopted to perform Chi- square test, COX's proportional Hazard Model, Life table survival analyses.
Of 111 patients, male 77 cases, female 34 cases, the median age was 55(14-85)years, CD10, BCL-6, MUM-1, BCL-2 positive rates were 15.7%(16/102), 58.8%(60/102), 33.0%(34/103), 74.8(77/103)respectively, the abnormal rate of BCL-2 gene was 43.1%(25/58, 24 cases with multiple copies, 1 case with translocation), and the abnormal rate of MYC gene was 20.4%(10/49, 10 cases with multiple copies). Coexistence of BCL-2 and MYC genes abnormalities accounted for 13.0%(6/46). According to the classification of Hans model, GCB subgroup accounted for 41.2%(42/102), and non-GCB subgroup 58.8%(60/102), the median survival time was 24 months, 3-year and 5-year overall survival rates were 48.5% and 39.7% respectively. Overall survival rates of normal and abnormal BCL-2 gene were 34.2%,22.8%, respectively with no statistical significance(P=0.770). Overall survival rates of normal and abnormal MYC gene were 35.9% and 22.2% ,with no statistical significance(P=0.650). Overall survival rate of double-hit was 0, far worse than that of single abnormal gene(P=0.034), which implied double-hit of BCL-2 and MYC gene abnormality to be adverse prognostic factors. BCL-6 protein express could be classified as benign prognostic factors, while ECOG score≥2, escalated IPI index as adverse prognostic factors, and further COX risk model regression analysis indicated that ECOG score, IPI grading and treatment methods were independently adverse factors affecting prognosis. Comprehensive therapy based on chemotherapy could improve outcome.
BCL-2/MYC genes double-hit was the factor for the adverse outcome in DLBCL patients. However, ECOG score, IPI risk grading and treatment methods were the independent factors affecting prognosis.
探讨BCL-2/MYC双打击对弥漫性大B细胞淋巴瘤(DLBCL)预后的影响。
进行一项回顾性研究,调查111例DLBCL患者的临床和病理数据。采用免疫组织化学方法检测CD10、BCL-6、MUM-1、BCL-2蛋白表达,对有足够病理数据的患者通过荧光原位杂交(FISH)分析BCL-2和MYC基因异常情况。采用SAS 8.2进行卡方检验、COX比例风险模型、寿命表生存分析。
111例患者中,男性77例,女性34例,中位年龄55(14 - 85)岁,CD10、BCL-6、MUM-1、BCL-2阳性率分别为15.7%(16/102)、58.8%(60/102)、33.0%(34/103)、74.8%(77/103),BCL-2基因异常率为43.1%(25/58,24例多拷贝,1例易位),MYC基因异常率为20.4%(10/49,10例多拷贝)。BCL-2和MYC基因异常共存占13.0%(6/46)。根据汉斯模型分类,生发中心B细胞(GCB)亚组占41.2%(42/102),非GCB亚组占58.8%(60/102),中位生存时间为24个月,3年和5年总生存率分别为48.5%和39.7%。BCL-2基因正常和异常患者的总生存率分别为34.2%、22.8%,差异无统计学意义(P = 0.770)。MYC基因正常和异常患者的总生存率分别为35.9%和22.2%,差异无统计学意义(P = 0.650)。双打击患者的总生存率为0,远低于单基因异常患者(P = 0.034),这表明BCL-2和MYC基因异常双打击是不良预后因素。BCL-6蛋白表达可归类为良性预后因素,而东部肿瘤协作组(ECOG)评分≥2、国际预后指数(IPI)升高为不良预后因素,进一步的COX风险模型回归分析表明,ECOG评分、IPI分级和治疗方法是影响预后的独立不良因素。基于化疗的综合治疗可改善预后。
BCL-2/MYC基因双打击是DLBCL患者不良预后的因素。然而,ECOG评分、IPI风险分级和治疗方法是影响预后的独立因素。