Immunohistochemical detection of ZAP-70 in 341 cases of non-Hodgkin and Hodgkin lymphoma
Immunohistochemical detection of ZAP-70 in 341 cases of non-Hodgkin and Hodgkin lymphoma
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DOI：
10.1038/modpathol.3800145
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发表时间：
2004-08-01
期刊：
影响因子：
7.5
通讯作者：
Medeiros, LJ
中科院分区：
文献类型：
--
作者：
Admirand, JH;Rassidakis, GZ;Medeiros, LJ
应用免疫组化方法检测341例非霍奇金淋巴瘤和霍奇金淋巴瘤中ZAP-70的表达。在B细胞NHL中，ZAP-70在6例前体B淋巴母细胞淋巴瘤中的5例（83%）、37例慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/ SLL）中的11例（30%）、39例套细胞淋巴瘤中的5例（13%）、12例Burkitt淋巴瘤中的1例（8%）和12例结边缘区B细胞淋巴瘤中的1例（8%）中阳性。在22例CLL/SLL中，9例IgV（H）基因未突变的患者中有7例（78%）表达ZAP-70，而13例IgV（H）基因突变的患者中有1例（13%）表达ZAP-70（P = 0.0015 Fisher精确检验）。在弥漫性大B细胞淋巴瘤（n=26）、粘膜相关淋巴组织结边缘区B细胞淋巴瘤（n = 24）、滤泡性淋巴瘤（n = 21）、浆细胞骨髓瘤/浆细胞瘤（n = 10）、淋巴浆细胞性淋巴瘤（n = 10）和脾边缘区淋巴瘤（n = 6）中未检测到ZAP-70表达。在T/NK细胞NHL中，ZAP-70在所有结节性自然杀伤（NK）/T细胞淋巴瘤、鼻型（n = 6）和肠病型T细胞淋巴瘤（n = 4）、皮下脂膜炎样T细胞淋巴瘤中的4/5（80%）、蕈样真菌病中的6/8（75%）、前体T淋巴母细胞淋巴瘤中的3/5（60%）、17例外周T细胞淋巴瘤中有10例（59%），4例母细胞性NK细胞淋巴瘤中有2例（50%），3例T细胞幼淋巴细胞白血病中有1例（33%），52例间变性大细胞淋巴瘤中有13例（25%），6例血管免疫母细胞性T细胞淋巴瘤中有1例（17%）。12例皮肤CD 30阳性淋巴组织增生性疾病中有7例（58%）也是ZAP-70阳性。在霍奇金淋巴瘤中，ZAP-70在所有测试病例的肿瘤细胞中均为阴性。ZAP-70在B细胞淋巴瘤和反应性T细胞中的染色主要是细胞核，具有可变的细胞质染色。相比之下，ZAP-70在T/NK细胞淋巴瘤中的染色是异质的，并且观察到从主要核染色到主要胞质染色的转变，特别是在具有高级别形态的那些肿瘤中。总之，ZAP-70在许多淋巴瘤类型中表达，与CLL/SLL中的免疫球蛋白重链可变区基因突变状态相关，并且可以使用免疫组织化学方法可靠地检测到。
Using immunohistochemical methods, we evaluated zeta-associated protein (ZAP)-70 expression in 341 cases of non-Hodgkin and Hodgkin lymphoma. In B-cell NHL, ZAP-70 was positive in five of six (83%) precursor B-lymphoblastic lymphoma, 11 of 37 (30%) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/ SLL), five of 39 (13%) mantle cell lymphoma, one of 12 (8%) Burkitt lymphoma, and one of 12 (8%) nodal marginal zone B-cell lymphoma. In 22 cases of CLL/SLL, seven of nine (78%) with unmutated IgV(H) genes expressed ZAP-70, compared with one of 13 (13%) with mutated IgV(H) genes (P = 0.0015 Fisher's exact test). ZAP-70 expression was not detected in diffuse large B-cell lymphoma (n=26), extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (n = 24), follicular lymphoma (n = 21), plasma cell myeloma/ plasmacytoma (n = 10), lymphoplasmacytic lymphoma (n = 10), or splenic marginal zone lymphoma (n = 6). In T/NK-cell NHL, ZAP-70 was positive in all extranodal natural killer (NK) /T-cell lymphoma, nasal-type (n = 6) and enteropathy-type T-cell lymphoma (n = 4), four of five (80%) subcutaneous panniculitis-like T-cell lymphoma, six of eight (75%) mycosis fungoides, three of five (60%) precursor T-lymphoblastic lymphoma, 10 of 17 (59%) peripheral T-cell lymphoma, two of four (50%) blastic NK-cell lymphoma, one of three (33%) T-cell prolymphocytic leukemia, 13 of 52 (25%) anaplastic large cell lymphoma, and one of six (17%) angioimmunoblastic T-cell lymphoma. Seven of 12 (58%) cutaneous CD30-positive lymphoproliferative disorders were also ZAP-70-positive. In Hodgkin lymphoma, ZAP-70 was negative in neoplastic cells in all cases tested. ZAP-70 staining in B-cell lymphomas and reactive T cells was predominantly nuclear with variable cytoplasmic staining. By contrast, ZAP-70 staining in T/NK-cell lymphomas was heterogeneous, and a shift from predominantly nuclear to predominantly cytoplasmic staining was observed, particularly in those neoplasms with high-grade morphology. In summary, ZAP-70 is expressed by many lymphoma types, correlates with immunoglobulin heavy-chain variable region gene mutational status in CLL/SLL, and can be detected reliably using immunohistochemical methods.