涎腺非霍奇金淋巴瘤相关基因表达及意义

Expression and clinic significance of gene-associated lymphoma of salivary glands

目的:分析涎腺非霍奇金淋巴瘤的临床病理特点,探讨其分子遗传学特征及意义。方法:依据2008年WHO肿瘤分类标准对标本重新诊断核实。采用IgH、MALT1、bcl-6、c-myc、bcl-2、CCND1、bcl-10、FOXP1双色分离重排探针、IgH/bcl-2双色融合易位探针和18号染色体着丝粒探针,利用间期萤光原位杂交(FISH)的方法检测32例涎腺非霍奇金淋巴瘤的分子遗传学特点。结果:32例淋巴瘤中黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(MALT淋巴瘤)28例(占87.5%),滤泡性淋巴瘤2例,弥漫性大B细胞淋巴瘤2例。60.7%(17/28)的涎腺MALT淋巴瘤携带分子遗传学异常。其中IgH基因断裂1例,但未找到与其发生相互易位的伙伴基因;基因3拷贝者16例,其中MALT1基因、bcl-6基因和c-myc基因3拷贝的发生率分别为25%(7/28)、43%(12/28)和7%(2/28)。16例基因3拷贝病例中,两种基因3拷贝合并存在者5例,其中bcl-6基因合并MALT1基因3拷贝者4例,bcl-6基因合并c-myc基因3拷贝者1例。进一步研究显示,MALT1基因3拷贝者均存在18号染色体三体。2例滤泡性淋巴瘤都携带t(14;18)(q32;q21)/IgH-bcl-2。2例弥漫性大B细胞性淋巴瘤均存在遗传异常,1例表现为bcl-6基因3拷贝合并18号染色体三体,另1例表现为bcl-6基因3拷贝合并IgH和c-myc基因双断裂。结论:MALT淋巴瘤是涎腺常见的淋巴瘤类型;间期FISH有助于淋巴瘤的分类;MALT1基因3拷贝者由18号染色体三体所致;18号染色体三体和bcl-6基因3拷贝(可能为3号染色体三体所致)是涎腺MALT淋巴瘤常见的分子遗传学异常。

Objective： To investigate clinicopathological and genetic characteristics of Lymphoma of salivary glands. Methods： Clinical, morphological and immunohistochemical feature of 32 cases of lymphoma in salivary glands were studied,including 5 cases of rective lymphoid hyperplasia and 32 lymphomas, retrospectivily. Classification of the lymphomas were made assording to the WHO classification of tumors of haemtopoietic and lymphoid tissues. All cases were studied with interphase fluorescence in situ hybridization （FISH） using dual color break apart probes of IgH, MALT1, bcl-6, c-myc, bcl-2, CCND1, bcl-lO, and F0XP1 for detection of chromosomal aberrations, involving IgH, MALT1, bcl-6, c-myc, bcl-2, cyclinD1, bcl-10 and FOXP1 gene, repectively. FISH with IgH/bcl-2 dual fusion probe was used for detection of t （14 ; 18）（q32; q21）/IgH-bcl-2. CEP18 sepctrum orange probe was used for detection of aneuploidy of the chromosome 18. Results： Among 32 cases of lymphoma, 28 cases （87.5%） were extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue （MALT lymphoma）, 2 cases were fol-licular lymphoma （FL） and 2 cases diffuse large B-cell lymphoma （DLBCL）. Among the 28 cases of MALT lymphoma, chromosomal aberration were found in 60.7% （17/28） with interphase FISH analysis. One case showed positive IgH break-apart signal with unknown partner,16 cases showed three copies of different genes, of which, three copies of MALT1, bcl-6, and c-myc were identified in 7 cases （25%）,12 cases （43%）,and 2 cases （8%） of MALT lymphomas, respectively. In addition, 5 cases showed two genes, including three copies of bcl-6 and MALT1 in 4 cases, and three copies of bcl-6 together with c-myc in one case. Furthermore,all cases with three copies of MALT1 had trisomy 18 （14; 18） （q32; q21） was detected in both follicular lymphomas.Of the 2 DLBCL cases, one showed three copies of bcl-6 together with trlsomyl8 and the other one showed three copies of bcl-6 together with IgH and c-myc rearrangements. Chromosomal aberration was not found in all 5 cases of reactive lymphoid hyperplasia. Conclusion： The most common entity of lymphoma of salivary gland is MALT lymphoma and FISH is helpful for their differential diagnosis and classification. Trisomy 18 and three copies of bcl-6 are common chromosomal aberrations in lymphoma of salivary glands.