Expression Profiles of MYC Protein and MYC Gene Rearrangement in Lymphomas
Expression Profiles of MYC Protein and MYC Gene Rearrangement in Lymphomas
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DOI：
10.1097/pas.0000000000000365
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发表时间：
2015-03-01
影响因子：
5.6
通讯作者：
Natkunam, Yasodha
中科院分区：
文献类型：
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作者：
Chisholm, Karen M.;Bangs, Charles D.;Natkunam, Yasodha
MYC易位是Burkitt淋巴瘤和一组预后较差的弥漫性大B细胞淋巴瘤(DLBCL)的典型特征。然而，在淋巴瘤中，MYC基因重排的临床相关性及其与MYC蛋白表达的关系尚未得到很好的描述。用抗MYC克隆Y69和双色分离荧光原位杂交探针检测MYC基因重排，成功地评估了包含1214个淋巴瘤的组织芯片。侵袭性B细胞淋巴瘤，包括Burkitt淋巴瘤和DLBCL，在50%的淋巴瘤细胞中MYC蛋白染色水平最高。相当比例的浆母细胞性、B淋巴母细胞性和T淋巴母细胞性、结外NK/T细胞淋巴瘤也有50%的细胞表达，而只有偶见浆细胞骨髓瘤、套细胞淋巴瘤和经典型霍奇金淋巴瘤有较高的表达。小B细胞淋巴瘤，当呈阳性时，50%的细胞中有MYC蛋白。在侵袭性B细胞淋巴瘤中，MYC重排与MYC免疫组织化学的符合率较高，但部分DLBCL和表达MYC蛋白的所有T细胞和NK细胞淋巴瘤缺乏MYC基因重排。我们的结果为淋巴瘤中MYC蛋白的表达提供了一个基线，并表明它的表达不是淋巴瘤亚型、细胞谱系或预期的临床行为所特有的，并且具有高度的变异性。此外，MYC蛋白的表达并不一定与MYC基因重排相关，提示在解释MYC免疫组织化学在淋巴瘤鉴别诊断中的作用时需要谨慎。
MYC translocations are a defining feature of Burkitt lymphoma and a group of diffuse large B-cell lymphoma (DLBCL) with inferior outcome. However, the clinical relevance of MYC gene rearrangement and its relationship with MYC protein expression has not been well characterized in lymphomas. Tissue microarrays containing 1214 lymphomas were successfully evaluated by immunohistochemistry using anti-MYC clone Y69 and a dual-color break-apart fluorescence in situ hybridization probe to detect MYC gene rearrangements. Aggressive B-cell lymphomas including Burkitt lymphoma and DLBCL showed the highest level of MYC protein staining defined as staining in > 50% of lymphoma cells. A significant proportion of plasmablastic, B-lymphoblastic and T-lymphoblastic, and extranodal NK/T-cell lymphomas also showed staining in > 50% of cells, whereas only occasional plasma cell myeloma, mantle cell lymphoma, and classical Hodgkin lymphoma showed a high level of staining. Small B-cell lymphomas, when positive, showed MYC protein in < 50% of cells. In aggressive B-cell lymphomas, MYC rearrangement and MYC immunohistochemistry showed a high concordance rate; however, some DLBCL and all T-cell and NK-cell lymphomas with MYC protein expression lacked MYC gene rearrangements. Our results provide a baseline for MYC protein expression in lymphomas and indicate that its expression is not specific to lymphoma subtypes, cell lineage, or expected clinical behavior and is highly variable. In addition, MYC protein expression is not necessarily correlated with MYC gene rearrangements and suggests the need for caution in the interpretation of MYC immunohistochemistry in the differential diagnosis of lymphomas.