Dei Tos A P, Doglioni C, Laurino L, Barbareschi M, Fletcher C D
Department of Histopathology, City Hospital, Feltre, Italy.
Histopathology. 1993 Jan;22(1):45-50. doi: 10.1111/j.1365-2559.1993.tb00068.x.
Alterations of the p53 tumour suppressor gene, with consequent nuclear p53 protein accumulation, are among the most common genetic lesions in human neoplasms. In the present paper we show p53 immunoreactivity in 65% of malignant and 21% of intermediate malignancy soft tissue tumours, and in 48% of benign/reactive soft tissue lesions. p53 immunoreactivity of sarcomas can be interpreted as an indirect indication of a mutation of the corresponding p53 gene, suggesting that its alteration may have a role in their pathogenesis. Our data on p53 immunoreactivity in benign lesions of the soft tissues are among the first demonstrations of p53 over-expression in benign/reactive conditions. We cannot exclude mutations of the p53 gene in these cases, but it is difficult to sustain this hypothesis in reactive/pseudoneoplastic lesions. Alternatively p53 immunoreactivity in benign processes could be due to an increase in wild-type p53 as a result of different physiological mechanisms (cell type-specific p53 regulation, cell maturation, DNA repair). Our results do not indicate that immunohistochemical demonstration of p53 expression is a marker of malignancy in soft tissue tumours and therefore is of limited use in differential diagnosis. However, they suggest the need for further molecular genetic studies in order to elucidate the biological significance of the abnormal expression of p53 in benign soft tissue lesions.
p53肿瘤抑制基因的改变以及随之而来的核p53蛋白积累,是人类肿瘤中最常见的基因损伤之一。在本文中,我们发现65%的恶性软组织肿瘤和21%的中度恶性软组织肿瘤以及48%的良性/反应性软组织病变中有p53免疫反应性。肉瘤的p53免疫反应性可被解释为相应p53基因发生突变的间接指征,这表明其改变可能在其发病机制中起作用。我们关于软组织良性病变中p53免疫反应性的数据是p53在良性/反应性情况下过度表达的首批证据之一。在这些病例中,我们不能排除p53基因的突变,但在反应性/假肿瘤性病变中很难支持这一假设。另外,良性病变中的p53免疫反应性可能是由于不同生理机制(细胞类型特异性p53调节、细胞成熟、DNA修复)导致野生型p53增加所致。我们的结果并不表明p53表达的免疫组化证明是软组织肿瘤恶性的标志物,因此在鉴别诊断中的用途有限。然而,它们表明需要进一步进行分子遗传学研究,以阐明p53在良性软组织病变中异常表达的生物学意义。