Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin's disease
Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin's disease
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DOI：
10.1046/j.1365-2141.2002.03456.x
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发表时间：
2002-05-01
影响因子：
6.5
通讯作者：
Gaidano, G
中科院分区：
文献类型：
--
作者：
Carbone, A;Gloghini, A;Gaidano, G
生物学和临床研究表明，霍奇金病（HD）可分为两大类，称为结节性淋巴细胞优势HD（NLP HD）和经典HD（CHD）。CHD分为四种亚型：结节硬化型、混合细胞型、淋巴细胞丰富型和淋巴细胞缺乏型。为了细化HD病理谱的组织发生，分析了75例CHD和13例NLP HD的MUM 1/IRF 4（多发性骨髓瘤-1/干扰素调节因子-4）的表达模式，MUM 1/IRF 4是IRF家族的淋巴细胞特异性成员，由晚期中心细胞和生发后中心（GC）B细胞表达。MUM 1与所有CHD病例（75/75例）的Hodgkin和Reed-Sternberg（HRS）细胞反应，具有中等至强的染色强度。相反，淋巴细胞和组织细胞（L & H）细胞，即NLP HD的推定肿瘤细胞，对MUM-1表达呈阴性（9/13例）或在< 10%的肿瘤细胞中对抗原显示弱反应性（4/13例）。在HD微环境中，NLP HD显示大量MUM 1阳性T淋巴细胞位于L & H细胞附近，而在CHD中，MUM 1阳性T淋巴细胞似乎随机分布，与HRS细胞没有特异性关系。总体而言，这项研究表明MUM 1在L & H细胞与HRS细胞中的表达不同，证实了NLP HD和CHD代表B细胞分化的不同阶段的观点。由于MUM 1阳性T淋巴细胞在NLP HD的肿瘤细胞周围形成rophilis，但不是CHD，这些数据也表明NLP HD和CHD的微环境存在差异，并假设MUM 1阳性T淋巴细胞与LH细胞的相互作用。
Biological and clinical studies have shown that Hodgkin's disease (HD) can be divided into two major categories, termed nodular lymphocyte predominance HD (NLP HD) and classic HD (CHD). Within CHD four subtypes have been distinguished: nodular sclerosis, mixed cellularity, lymphocyte rich and lymphocyte depletion. To refine the histogenesis of the pathological spectrum of HD, 75 CHD and 13 NLP HD were analysed for the expression pattern of MUM1/IRF4 (Multiple Myeloma-1/Interferon Regulatory Factor-4), a lymphocyte-specific member of the IRF family, that is expressed by late centrocytes and post-germinal centre (GC) B cells. MUM1 reacted with Hodgkin's and Reed-Sternberg (HRS) cells of all CHD cases (75/75 cases), with a moderate to strong staining intensity. Conversely, lymphocyte and histiocyte (L & H) cells, the putative tumour cells of NLP HD, were negative for MUM-1 expression (9/13 cases) or displayed a weak reactivity for the antigen in < 10% neoplastic cells (4/13 cases). With respect to HD microenvironment, NLP HD displayed numerous MUM1-positive T lymphocytes located in close proximity to L & H cells whereas, in CHD, MUM1-positive T lymphocytes appeared to be distributed randomly with no specific relationship with HRS cells. Overall, this study shows that MUM1 expression differs in L & H cells versus HRS cells, corroborating the notion that NLP HD and CHD represent different stages of B-cell differentiation. As MUM1-positive T lymphocytes form rosettes around tumour cells of NLP HD, but not of CHD, these data point also to differences in the microenvironment of NLP HD and CHD, and postulate an interactive role of MUM1-positive T lymphocytes with L H cells.