Sánchez-Beato M, Sáez A I, Martínez-Montero J C, Sol Mateo M, Sánchez-Verde L, Villuendas R, Troncone G, Piris M A
Department of Pathology, Virgen de la Salud Hospital, Toledo, Spain.
Am J Pathol. 1997 Jul;151(1):151-60.
Cell cycle progression is regulated by the combined action of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CDKIs). p27KIP1, which has a high degree of similarity with p21WAF1, is a general CDKI thought to be involved in G1 arrest in response to agents that inhibit cell cycle progression. The aims of this study were 1) to establish the pattern of expression of p27KIP1 protein in nontumor lymphoid tissue, 2) to determine whether p27KIP1 is involved in lymphomagenesis, and 3) to address the possible relationship between p27KIP1 and p21WAF1 expression in reactive and tumor lymphoid tissue. p27KIP1 protein was found to be mainly present in quiescent lymphocytes in reactive lymphoid tissue as well as in peripheral blood lymphocytes, with an inverse expression for p27KIP1 and Ki-67 proteins. The same p27KIP1 expression pattern was observed in lymphomas, independently of histological type; small resting cells were p27KIP1 positive, and large proliferating cells were p27KIP1 negative. Therefore, tumors with a low proliferative index were mostly positive, whereas tumors characterized by a higher growth fraction bad low p27KIP1 protein levels. An unexpected finding was the existence of a group of six cases of high-grade lymphomas (three diffuse large B-cell lymphomas and three Burkitt's lymphomas) with homogeneously strong staining for p27KIP1 protein. All 6 of these cases belong to a group of 28 cases characterized by blockage of the p53 tumor suppressor pathway, as determined by genetic (p53 mutation) or immunophenotypic studies (p53+/p21-). p27KIP1 expression was not seen in any case of aggressive non-Hodgkin's lymphoma with an intact p53 pathway. The results indicate that p27KIP1 is down-regulated in lymphomas with a high proliferative index, although it is highly expressed in high-grade lymphomas with defects in the p53 pathway.
细胞周期进程受细胞周期蛋白、细胞周期蛋白依赖性激酶（CDK）和CDK抑制剂（CDKI）的共同作用调控。p27KIP1与p21WAF1具有高度相似性，是一种普遍认为参与G1期阻滞以响应抑制细胞周期进程因子的CDKI。本研究的目的是：1）确定p27KIP1蛋白在非肿瘤性淋巴组织中的表达模式；2）确定p27KIP1是否参与淋巴瘤的发生；3）探讨反应性和肿瘤性淋巴组织中p27KIP1与p21WAF1表达之间的可能关系。发现p27KIP1蛋白主要存在于反应性淋巴组织中的静止淋巴细胞以及外周血淋巴细胞中，p27KIP1和Ki-67蛋白呈反向表达。在淋巴瘤中观察到相同的p27KIP1表达模式，与组织学类型无关；小的静止细胞p27KIP1阳性，大的增殖细胞p27KIP1阴性。因此，增殖指数低的肿瘤大多为阳性，而以高生长分数为特征的肿瘤p27KIP1蛋白水平低。一个意外发现是有一组6例高级别淋巴瘤（3例弥漫性大B细胞淋巴瘤和3例伯基特淋巴瘤），p27KIP1蛋白呈均匀强染色。通过基因（p53突变）或免疫表型研究（p53+/p21-）确定，所有这6例均属于一组28例以p53肿瘤抑制途径阻断为特征的病例。在任何p53途径完整的侵袭性非霍奇金淋巴瘤病例中均未观察到p27KIP1表达。结果表明，p27KIP1在增殖指数高的淋巴瘤中下调，尽管它在p53途径有缺陷的高级别淋巴瘤中高表达。
