Clinicopathologic, molecular pathologic and biologic study of malignant lymphoma

对套细胞淋巴瘤(MCL)、原发胃B细胞淋巴瘤(PGL)、CD56(NCAM)阳性的血管中心性淋巴瘤(ACL)和鼻腔T/NK细胞淋巴瘤(NTCL)的临床病理、分子病理学和生物学特性进行了研究。我们制备了一种针对重组PRAD1/细胞周期蛋白D1产物的单抗5D4，结果表明，细胞周期蛋白D1蛋白的免疫定位是诊断恶性淋巴瘤的重要指标。我们根据粘膜相关淋巴组织低度B细胞淋巴瘤(MALT)的概念提出的PGL的组织学分型与生长形态、病理分期、预后以及BC12和p53等癌基因的表达有关。在爱知癌症中心的登记病例中，也发现了10例CD56阳性的ACL患者，构成了一个独特的组，其特点是血管中心性、嗜天青颗粒、假定的自然杀伤(NK)细胞系和侵袭性行为。此外，本研究支持NTCL是一种与其他T细胞淋巴瘤不同的EB病毒相关肿瘤。这些数据可能为阐明日本人恶性淋巴瘤的疾病谱提供依据。在这项研究的过程中，也强调了位于灰区的淋巴增生性疾病的进一步调查。

Several entities of non-Hodgkin's lymphoma, i.e., mantle cell lymphoma (MCL), primary gastric B-cell lymphoma (PGL), CD56 (NCAM) -positive angiocentric lymphoma (AcL), and nasal T/NK-cell lymphomas (NTCL), were investigated on their clinicopathologic, molecular pathologic and biologic aspects. We produced a monoclonal antibody, 5D4, against a recombinant PRAD1/cyclin D1 product, and revealed that the immunolocalization of cyclin D1 protein is an essential marker for the definite diagnosis of MCL.The patients with cyclin D1 overexpressing lymphomas appeared to consitute a very homogeneous group, the 5-year survival rate being 11%. The histological typing of PGL,which was proposed by us on the basis of the concept of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), showed to correlate with growth appearance, pathologic stage, prognosis, and expression of several oncogenes such as bc12 and p53.10 patients with CD56-positive AcLs were also identified among the registered cases in Aichi Cancer Center, constituting a distinct group characterized by angiocentricity, azurophilic granules, putative natural killer (NK) -cell lineage, and aggressive behavior. Furthermore, the present study supported that NTCL is identified as Epstein-Barr virus-associated tumors distinct from the other T-cell lymphoma. These date may provide the basis for clarifying the disease spectrum of malignant lymphomas in the Japanese patients. During the process of this study, further investigation of lymphoproliferative disorders located at the gray zone was also emphasized.