中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2013年
2期
143-147
,共5页
韩永胜%薛永权%杨海燕%张俊%潘金兰
韓永勝%薛永權%楊海燕%張俊%潘金蘭
한영성%설영권%양해연%장준%반금란
弥漫性大B细胞淋巴瘤%免疫分型%荧光原位杂交%预后
瀰漫性大B細胞淋巴瘤%免疫分型%熒光原位雜交%預後
미만성대B세포림파류%면역분형%형광원위잡교%예후
Diffuse large B-cell Lymphoma%Immunophenotyping%Fluorescence in situ hybridization%Prognosis
目的 分析弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)的免疫表型分型和分子遗传学异常,并探讨二者之间的相关性及其对于预后的意义.方法 用免疫组织化学链霉亲和素-过氧化物酶法检测59例DLBCL患者中CD10、BCL6、MUM1的表达,采用Hans免疫分型法将DLBCL分为生发中心B细胞(germinal center B-cell,GCB)型和非GCB型；分别应用BCL6双色断裂点分离探针、IgH/BCL2双色双融合探针及MYC双色断裂点分离探针在石蜡包埋的淋巴瘤组织切片上进行荧光原位杂交分析,检测BCL6、BCL2和MYC基因的易位和扩增情况.结果 在59例DLBCL患者中,GCB型占28.8％(17/59),非GCB型占71.2％ (42/59).BCL6、BCL2和MYC基因易位的发生率分别为24.1％(14/58)、1.7％(1/59)和5.3％(3/57),BCL6、BCL2和MYC基因扩增的发生率分别为17.2％ (10/58)、22.0％(13/59)和21.1％(12/57).BCL6扩增与BCL6易位无相关性(P=0.424),但与BCL2及MYC扩增呈正相关(列联系数C值分别为0.405和0.403,P值均＜0.01).在GCB型中BCL6易位的发生率高于非GCB型,而BCL6、BCL2或MYC扩增更常见于非GCB型,差异接近但均无统计学意义(P值分别为0.089和0.106).在单因素分析中,免疫分型和国际预后指数积分对总生存率(overall survival,OS)均有显著影响(P值分别为0.047和0.001),而BCL6易位和3基因扩增对OS率均无明显影响(P值分别为0.150和0.444)；在多因素分析中,国际预后指数积分是影响OS唯一的独立预后因素(RR=3.843,P=0.017).结论 本组DLBCL患者中GCB亚型较少见,常见的遗传学异常为BCL6易位和BCL6、BCL2及MYC扩增,且3基因扩增之间密切相关,而BCL2易位的发生率低.免疫表型分型对预后的预测意义较小,遗传学异常不能用于预测DLBCL患者的预后.
目的 分析瀰漫性大B細胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)的免疫錶型分型和分子遺傳學異常,併探討二者之間的相關性及其對于預後的意義.方法 用免疫組織化學鏈黴親和素-過氧化物酶法檢測59例DLBCL患者中CD10、BCL6、MUM1的錶達,採用Hans免疫分型法將DLBCL分為生髮中心B細胞(germinal center B-cell,GCB)型和非GCB型；分彆應用BCL6雙色斷裂點分離探針、IgH/BCL2雙色雙融閤探針及MYC雙色斷裂點分離探針在石蠟包埋的淋巴瘤組織切片上進行熒光原位雜交分析,檢測BCL6、BCL2和MYC基因的易位和擴增情況.結果 在59例DLBCL患者中,GCB型佔28.8％(17/59),非GCB型佔71.2％ (42/59).BCL6、BCL2和MYC基因易位的髮生率分彆為24.1％(14/58)、1.7％(1/59)和5.3％(3/57),BCL6、BCL2和MYC基因擴增的髮生率分彆為17.2％ (10/58)、22.0％(13/59)和21.1％(12/57).BCL6擴增與BCL6易位無相關性(P=0.424),但與BCL2及MYC擴增呈正相關(列聯繫數C值分彆為0.405和0.403,P值均＜0.01).在GCB型中BCL6易位的髮生率高于非GCB型,而BCL6、BCL2或MYC擴增更常見于非GCB型,差異接近但均無統計學意義(P值分彆為0.089和0.106).在單因素分析中,免疫分型和國際預後指數積分對總生存率(overall survival,OS)均有顯著影響(P值分彆為0.047和0.001),而BCL6易位和3基因擴增對OS率均無明顯影響(P值分彆為0.150和0.444)；在多因素分析中,國際預後指數積分是影響OS唯一的獨立預後因素(RR=3.843,P=0.017).結論 本組DLBCL患者中GCB亞型較少見,常見的遺傳學異常為BCL6易位和BCL6、BCL2及MYC擴增,且3基因擴增之間密切相關,而BCL2易位的髮生率低.免疫錶型分型對預後的預測意義較小,遺傳學異常不能用于預測DLBCL患者的預後.
목적 분석미만성대B세포림파류(diffuse large B-cell lymphoma,DLBCL)적면역표형분형화분자유전학이상,병탐토이자지간적상관성급기대우예후적의의.방법 용면역조직화학련매친화소-과양화물매법검측59례DLBCL환자중CD10、BCL6、MUM1적표체,채용Hans면역분형법장DLBCL분위생발중심B세포(germinal center B-cell,GCB)형화비GCB형；분별응용BCL6쌍색단렬점분리탐침、IgH/BCL2쌍색쌍융합탐침급MYC쌍색단렬점분리탐침재석사포매적림파류조직절편상진행형광원위잡교분석,검측BCL6、BCL2화MYC기인적역위화확증정황.결과 재59례DLBCL환자중,GCB형점28.8％(17/59),비GCB형점71.2％ (42/59).BCL6、BCL2화MYC기인역위적발생솔분별위24.1％(14/58)、1.7％(1/59)화5.3％(3/57),BCL6、BCL2화MYC기인확증적발생솔분별위17.2％ (10/58)、22.0％(13/59)화21.1％(12/57).BCL6확증여BCL6역위무상관성(P=0.424),단여BCL2급MYC확증정정상관(렬련계수C치분별위0.405화0.403,P치균＜0.01).재GCB형중BCL6역위적발생솔고우비GCB형,이BCL6、BCL2혹MYC확증경상견우비GCB형,차이접근단균무통계학의의(P치분별위0.089화0.106).재단인소분석중,면역분형화국제예후지수적분대총생존솔(overall survival,OS)균유현저영향(P치분별위0.047화0.001),이BCL6역위화3기인확증대OS솔균무명현영향(P치분별위0.150화0.444)；재다인소분석중,국제예후지수적분시영향OS유일적독립예후인소(RR=3.843,P=0.017).결론 본조DLBCL환자중GCB아형교소견,상견적유전학이상위BCL6역위화BCL6、BCL2급MYC확증,차3기인확증지간밀절상관,이BCL2역위적발생솔저.면역표형분형대예후적예측의의교소,유전학이상불능용우예측DLBCL환자적예후.
Objective To perform immunophenotyping and molecular genetic analysis for diffuse large B-cell lymphoma (DLBCL),and to explore their correlation and implication for prognosis.Methods Immunohistochemical streptavidin peroxidase (SP) method was used to determine the expression of CD10,BCL6 and MUM1 in 59 cases of DLBCL.A Hans algorithm was used to classify DLBCL into germinal center B-cell (GCB) and non-GCB subtypes.Interphase fluorescence in situ hybridization (FISH) assay was performed on paraffin-embedded lymphoma tissue sections to detect translocations and amplifications of BCL6,BCL2 and MYC genes with dual-color break-apart BCL6 probe,dual-color dual-fusion IgH/BCL2 probe and dual-color break-apart MYC probe,respectively.Results In the 59 cases of DLBCL,28.8％ (17/59) belonged to GCB subtype,and 71.2％ (42/59) belonged to non-GCB subtype.The incidences of BCL6,BCL2 and MYC gene translocations were 24.1％ (14/58),1.7％ (1/59) and 5.3％ (3/57),respectively.The incidences of BCL6,BCL2 and MYC gene amplifications were 17.2％ (10/58),22.0％ (13/59) and 21.1％ (12/57),respectively.BCL6 amplification was not correlated withBCL6 translocation (P=0.424),but was correlated with amplifications of BCL2 and MYC (C=0.405 and 0.403,respectively,P＜0.01).The incidence of BCL6 translocation in GCB type was higher than that in non-GCB type,and amplifications of BCL6,BCL2 or MYC were more frequently encountered in non-GCB type,though no statistical significance was detected (P =0.089 and 0.106,respectively).By univariate analysis,immunophenotyping and international prognostic index (IPI) exerted a significant effect on overall survival (OS) (P=0.047 and 0.001,respectively),but to which BCL6 translocation and amplification of the 3 genes were not related (P=0.150 and 0.444,respectively).By multivariate analysis,IPI score was the only independent prognostic factor for OS (RR =3.843,P=0.017).Conclusion The GCB subtype of DLBCL is less common in the patient cohort.Common genetic aberrations include BCL6 translocation and BCL6,BCL2 and MYC amplifications.Amplification of the 3 genes is strongly correlated with each other,and the incidence of BCL2 translocation is low.Immunophenotyping only has minor significance for the prognosis.Genetic aberrations cannot predict the clinical outcome of DLBCL.
