Chisholm KM, Bangs CD, Bacchi CE, et al.Expression Profiles of MYC Protein and MYC Gene Rearrangement in Lymphomas. Am J Surg Pathol. 2015,[Epub ahead of print]
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.
MYC易位是伯基特淋巴瘤（BL）和一组弥漫大B细胞性淋巴瘤（DLBCL）的最典型特征，预后相对较差。然而在淋巴瘤中仍未阐明MYC基因重排与临床关联，及其与MYC蛋白表达情况的相关性。采用组织微阵列技术，通过免疫组织化学法，利用抗MYC单克隆抗体Y69和双重分离荧光原位杂交探针对1214个淋巴瘤进行了MYC基因重排的检测。结果侵袭性B细胞淋巴瘤（BL和DLBCL）显示了较高水平的MYC蛋白着色，大于50%的瘤细胞着色；很大一部分浆母细胞性淋巴瘤、B或T细胞淋巴母细胞性淋巴瘤和结外NK/T细胞性淋巴瘤显示了大于50%的瘤细胞MYC蛋白着色，只有极少数的浆细胞骨髓瘤、套细胞淋巴瘤和经典的霍奇金淋巴瘤表现出较高水平的染色；当小B细胞性淋巴瘤中出现MYC蛋白着色时，小于50%的瘤细胞阳性。在侵袭性B细胞淋巴瘤中，MYC重排和MYC免疫组化显示了较高的一致性，然而一些DLBCL和所有的伴MYC蛋白表达的T细胞和NK细胞淋巴瘤却缺乏MYC基因的重排。作者的研究结果指出了MYC蛋白在淋巴瘤中的表达概况，并表明其表达并不特定于淋巴瘤亚型和细胞谱系，并与可预测的临床行为无关。另外，MYC蛋白的表达不一定与MYC基因重排有关，因此有必要高度谨慎说明MYC蛋白免疫组化在淋巴瘤鉴别诊断中的作用。