Piris M A, Pezzella F, Martinez-Montero J C, Orradre J L, Villuendas R, Sanchez-Beato M, Cuena R, Cruz M A, Martinez B, Pezella F [corrected to Pezzella F ]
Department of Pathology, Hospital Virgen de la Salud, Toledo, Spain.
Br J Cancer. 1994 Feb;69(2):337-41. doi: 10.1038/bjc.1994.61.
B-cell high-grade lymphomas are heterogeneous in terms of histology, clinical presentation, treatment response and prognosis. As bcl-2 and p53 gene deregulations are frequently involved in several types of lymphoid malignancies, we aimed our investigation at the study of the relation between bcl-2 and p53 expression and survival probability in a group of 119 patients with B-cell high-grade lymphoma. These were obtained from the Virgen de la Salud Hospital, Toledo, Spain (73 cases), John Radcliffe Hospital, Oxford, UK (31 cases), and the Istituto Nazionale dei Tumori, Milan, Italy (15 cases). The relation between bcl-2 protein expression and survival was small, depending on the primary localisation of the tumour (in lymph node of mucosae), and lacked a significant correlation with overall survival. In contrast with this, p53 expression was related to survival probability in our series, this relation being both significant and independent of histological diagnosis. p53-positive patients showed a sudden decrease in life expectancy in the first months after diagnosis. Multivariant regression analysis confirmed that the only parameters significantly related with survival were extranodal origin, which is associated with a better prognosis, and p53 expression, which indicates a poor prognosis. Simultaneous expression of bcl-2 and p53 was associated with a poorer prognosis than p53 alone. This is particularly significant for large B-cell lymphomas presenting in lymph nodes. The cumulative poor effect of both p53 and bcl-2 in large B-cell lymphomas, which is more significant in nodal tumours, could confirm the existence of a multistep genetic deregulation in non-Hodgkin's lymphoma. This indicates that the genetic mechanisms controlling apoptosis and their disregulation are critical steps in the progression of lymphomas.
B 细胞高级别淋巴瘤在组织学、临床表现、治疗反应和预后方面具有异质性。由于bcl-2和p53基因失调经常涉及多种类型的淋巴恶性肿瘤，我们针对119例B细胞高级别淋巴瘤患者，研究bcl-2和p53表达与生存概率之间的关系。这些病例来自西班牙托莱多市的维森德拉萨卢德医院（73例）、英国牛津的约翰·拉德克利夫医院（31例）以及意大利米兰的国家肿瘤研究所（15例）。bcl-2蛋白表达与生存之间的关系较小，这取决于肿瘤的原发部位（在黏膜淋巴结中），且与总生存缺乏显著相关性。与此相反，在我们的研究系列中，p53表达与生存概率相关，这种关系既显著又独立于组织学诊断。p53阳性患者在诊断后的头几个月预期寿命会突然下降。多变量回归分析证实，与生存显著相关的唯一参数是结外起源（与较好的预后相关）和p53表达（表明预后不良）。bcl-2和p53的同时表达与单独p53表达相比，预后更差。这对于发生在淋巴结的大B细胞淋巴瘤尤为显著。p53和bcl-2在大B细胞淋巴瘤中的累积不良影响，在淋巴结肿瘤中更为显著，这可能证实了非霍奇金淋巴瘤中存在多步骤基因失调。这表明控制细胞凋亡的遗传机制及其失调是淋巴瘤进展中的关键步骤。
