Significance of cyclin D1 overexpression for the diagnosis of mantle cell lymphoma: a clinicopathologic comparison of cyclin D1-positive MCL and cyclin D1-negative MCL-like B-cell lymphoma.
Significance of cyclin D1 overexpression for the diagnosis of mantle cell lymphoma: a clinicopathologic comparison of cyclin D1-positive MCL and cyclin D1-negative MCL-like B-cell lymphoma.
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DOI：
10.1182/blood.v95.7.2253
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发表时间：
2000-04
期刊：
影响因子：
20.3
通讯作者：
Y. Yatabe;R. Suzuki;K. Tobinai;Y. Matsuno;R. Ichinohasama;M. Okamoto;M. Yamaguchi;J. Tamaru;N. Uike;Y. Hashimoto;Y. Morishima;T. Suchi;M. Seto;S. Nakamura
中科院分区：
文献类型：
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作者：
Y. Yatabe;R. Suzuki;K. Tobinai;Y. Matsuno;R. Ichinohasama;M. Okamoto;M. Yamaguchi;J. Tamaru;N. Uike;Y. Hashimoto;Y. Morishima;T. Suchi;M. Seto;S. Nakamura
套细胞淋巴瘤(MCL)是一种独特的非霍奇金淋巴瘤的临床病理特征，以中小型淋巴细胞单调增殖，CD5和CD20共表达为特征，临床病程侵袭性强，不治之症，常有t(11；14)(q13；q32)易位。我们从细胞周期蛋白D1过度表达的角度对151例具有MCL形态的淋巴瘤进行了检测，这一点现在很容易被免疫组织化学检测到。细胞周期蛋白D1阳性128例(85%)，阴性23例(15%)。除了细胞周期蛋白D1免疫组织化学，目前的诊断方法，包括形态学和表型检查，都不能做出这种区分。尽管Cyclin D1阳性组和阴性组均以男性为主、疾病分期较晚、结外转移频繁、CD23反应性低为特征，但Cyclin D1阳性组的年龄分布(P=0.04)、细胞体积(P=0.02)、核分裂指数(P=0.01)、胃肠道受累(P=0.05)、国际预后指数(P=0.05)较高，p27(KIP1)表达较低(P<；0.0001)。特别值得注意的是，Cyclin D1阳性的MCL的生存率明显低于Cyclin D1阴性的淋巴瘤(5年生存率：30%对86%，P=.0002)，经多因素分析证实，这一点与其他危险因素无关。这些数据表明，Cyclin D1阳性和阴性组可能代表不同的实体，前者非常符合经典的典型MCL的特征。因此，我们建议将细胞周期蛋白D1阳性作为MCL的标准之一，并在新标准的基础上探索这种不治之症的创新治疗方法。
Mantle cell lymphoma (MCL) is a distinct clinicopathologic entity of non-Hodgkin's lymphoma, characterized by a monotonous proliferation of small to medium-sized lymphocytes with co-expression of CD5 and CD20, an aggressive and incurable clinical course, and frequent t(11;14)(q13;q32) translocation. We examined 151 cases of lymphoma with MCL morphology from a viewpoint of cyclin D1 overexpression, which is now easily detectable by immunohistochemistry. 128 cases (85%) showed positive nuclear staining for cyclin D1, while the remaining 23 (15%) were negative. Except for cyclin D1 immunohistochemistry, current diagnostic methods, including morphological and phenotypical examinations, could not make this distinction. Although both the cyclin D1-positive and -negative groups were characterized by male predominance, advanced stages of the disease, frequent extranodal involvement, and low CD23 reactivity, the cyclin D1-positive group showed a higher age distribution (P =.04), larger cell size (P =.02), higher mitotic index (P =.01), more frequent gastrointestinal involvement (P =.05), higher international prognostic index score (P =.05), and lower p27(KIP1) expression (P <.0001). Of particular interest is that cyclin D1-positive MCL showed significantly worse survival than cyclin D1-negative lymphoma (5-year survival: 30% versus 86%, P =.0002), which was confirmed by multivariate analysis to be independent of other risk factors. These data suggest that cyclin D1-positive and -negative groups may represent different entities and that the former closely fits the characteristics of classical, typical MCL. We therefore propose that cyclin D1-positivity should be included as one of the standard criteria for MCL, and that innovative therapies for this incurable disease should be explored on the basis of the new criteria.