Petit B, Leroy K, Kanavaros P, Boulland M L, Druet-Cabanac M, Haioun C, Bordessoule D, Gaulard P
Département de Pathologie, Hôpital Henri Mondor, Créteil, France.
Hum Pathol. 2001 Feb;32(2):196-204. doi: 10.1053/hupa.2001.21569.
To determine if p53 abnormalities could be involved in the pathogenesis of T- or natural killer (NK)-cell lymphomas, we investigated 51 cases of these lymphomas for the expression of p53 and its relationship with p53 gene mutations, the expression of the p21 protein as well as the proliferative and apoptotic indices. Overexpression of p53 was found in 19 cases (37%), whereas mutations of the p53 gene were observed in only 5 of 28 tested cases. The analysis of immunohistochemical data showed some entity-related phenotypic profiles. Anaplastic large cell lymphomas showed a frequent overexpression of p53 (7/8 cases) and p21 (6/8 cases) proteins and rare p53 mutations (1/7 cases), suggesting accumulation of a functional wild type p53 protein able to induce p21 expression. Nodal peripheral T-cell lymphomas unspecified showed relatively frequent overexpression of p53 protein (5/7 cases), infrequent p21 expression (2/7 cases), and rare p53 gene mutations (1/6 cases). In angioimmunoblastic lymphomas, the common phenotype was p53-/p21- (15/17 cases), with only a few scattered p53-positive cells, which, on the basis of double staining results, were mostly Epstein-Barr virus-infected B cells. A p53 gene mutation was only found in 1 case (1/8 cases) of angioimmunoblastic lymphoma, which showed cytologic tumor progression. Mycosis fungoides showed p53 overexpression in 2 of 4 cases, including 1 case with p53 gene mutation and features of cytologic tumor progression. Nasal NK/T lymphomas showed p53 overexpression in 2 of 5 cases, 1 of which had a p53 gene mutation. Finally, all lymphoblastic T-cell lymphomas (5 cases) and gammadelta hepatosplenic T-cell lymphomas (3 cases) were negative for expression of p53 and p21 proteins. We conclude that p53 protein overexpression is a common finding in some entities of T- and T/NK-cell lymphomas, whereas a p53 gene mutation is a rare, sporadic, and rather late event associated with tumor progression in some instances. The p53/p21 expression pattern appears to be variable in T- and T/NK-cell lymphoma entities, reinforcing the concept of distinct, entity-related mechanisms of pathogenesis in these tumors.
为了确定p53异常是否可能参与T细胞或自然杀伤（NK）细胞淋巴瘤的发病机制，我们研究了51例此类淋巴瘤中p53的表达及其与p53基因突变、p21蛋白表达以及增殖和凋亡指数的关系。19例（37%）发现p53过表达，而在28例检测病例中仅5例观察到p53基因突变。免疫组化数据分析显示了一些与实体相关的表型特征。间变性大细胞淋巴瘤显示p53（7/8例）和p21（6/8例）蛋白频繁过表达，p53突变罕见（1/7例），提示能够诱导p21表达的功能性野生型p53蛋白积聚。未特指的结内外周T细胞淋巴瘤显示p53蛋白相对频繁过表达（5/7例），p21表达不常见（2/7例），p53基因突变罕见（1/6例）。在血管免疫母细胞性淋巴瘤中，常见表型为p53-/p21-（15/17例），仅有少数散在的p53阳性细胞，根据双重染色结果，这些细胞大多为感染爱泼斯坦-巴尔病毒的B细胞。仅在1例（1/8例）血管免疫母细胞性淋巴瘤中发现p53基因突变，该病例显示细胞学肿瘤进展。蕈样肉芽肿在4例中有2例显示p53过表达，其中1例有p53基因突变及细胞学肿瘤进展特征。鼻NK/T淋巴瘤在5例中有2例显示p53过表达，其中1例有p53基因突变。最后，所有淋巴母细胞性T细胞淋巴瘤（5例）和γδ肝脾T细胞淋巴瘤（3例）的p53和p21蛋白表达均为阴性。我们得出结论，p53蛋白过表达在某些T细胞和T/NK细胞淋巴瘤实体中是常见现象，而p53基因突变是罕见的、散发性的，且在某些情况下与肿瘤进展相关的较晚期事件。p53/p21表达模式在T细胞和T/NK细胞淋巴瘤实体中似乎存在差异，强化了这些肿瘤存在独特的、与实体相关的发病机制这一概念。
