Kurtkaya-Yapicier Ozlem, Scheithauer Bernd W, Hebrink Deanne, James Charles D
Department of Pathology, Marmara University School of Medicine, Istanbul, Turkey.
Neurosurgery. 2002 Nov;51(5):1246-54; discussion 1254-5. doi: 10.1097/00006123-200211000-00021.
Immunostaining for p53 commonly is considered a marker of neoplasia. Previous studies of nonneoplastic processes have yielded conflicting results.
To test the assumption that p53 immunoreactivity indicates neoplasia, we examined 60 formalin-fixed, paraffin-embedded biopsies of nonneoplastic central nervous system lesions, including gliosis (n = 12), infarction (n = 9), demyelinating disease (n = 23), progressive multifocal leukoencephalopathy (n = 11), and herpes simplex virus encephalitis (n = 5). Diffuse astrocytomas (n = 50) of World Health Organization Grades 2 to 4 also were studied, as were six control autopsy brains. The avidin-biotin-peroxidase complex method was used with commercially available monoclonal antisera to both p53 (clone DO7; Dako, Carpinteria, CA) and mdm2 (Dako), a protein known to stabilize p53. Two samples of each nonneoplastic lesion also were subjected to deoxyribonucleic acid isolation, amplification, and sequencing of exons 5 to 8 of TP53.
Although it was low level in most instances, p53 immunoreactivity was noted in all but normal control samples. In reactive lesions, staining was largely observed in astrocytes and histiocytes. Scant oligodendroglia also were labeled in demyelinating disease. The progressive multifocal leukoencephalopathy samples revealed exceptionally strong staining in astrocytes and infected oligodendrocytes. Staining also was noted in occasional endothelial cells and neurons, and in rare lymphocytes. Immunoreactivity for mdm2, studied only in nonneoplastic lesions, was moderate to strong in all cases and limited to reactive astrocytes and histiocytes. No TP53 mutations were noted in the nonneoplastic lesions studied. To some extent, all astrocytomas exhibited p53 immunopositivity, particularly high-grade lesions.
p53 immunoreactivity is not limited to astrocytomas, but it can be observed in lesions that often are mistaken for glioma. No TP53 mutations accompany p53 expression in nonneoplastic lesions, and mdm2 may be responsible for persistence of p53 expression in these processes.
p53免疫染色通常被认为是肿瘤形成的标志物。先前对非肿瘤性病变的研究结果相互矛盾。
为了验证p53免疫反应性表明肿瘤形成这一假设，我们检查了60例非肿瘤性中枢神经系统病变的福尔马林固定、石蜡包埋活检组织，包括胶质增生（n = 12）、梗死（n = 9）、脱髓鞘疾病（n = 23）、进行性多灶性白质脑病（n = 11）和单纯疱疹病毒性脑炎（n = 5）。还研究了50例世界卫生组织2至4级的弥漫性星形细胞瘤，以及6个对照尸检脑。采用抗生物素蛋白-生物素-过氧化物酶复合物法，使用市售针对p53（克隆DO7；Dako，加利福尼亚州卡平特里亚）和mdm2（Dako）的单克隆抗血清，mdm2是一种已知可稳定p53的蛋白质。每个非肿瘤性病变的两个样本也进行了脱氧核糖核酸分离、扩增以及TP53外显子5至8的测序。
尽管在大多数情况下水平较低，但除正常对照样本外，所有样本均观察到p53免疫反应性。在反应性病变中，染色主要见于星形胶质细胞和组织细胞。在脱髓鞘疾病中，少量少突胶质细胞也被标记。进行性多灶性白质脑病样本在星形胶质细胞和受感染的少突胶质细胞中显示出异常强烈的染色。在偶尔的内皮细胞和神经元以及罕见的淋巴细胞中也观察到染色。仅在非肿瘤性病变中研究的mdm2免疫反应性在所有病例中为中度至强，且仅限于反应性星形胶质细胞和组织细胞。在所研究的非肿瘤性病变中未发现TP53突变。在某种程度上，所有星形细胞瘤均表现出p53免疫阳性，尤其是高级别病变。
p53免疫反应性不仅限于星形细胞瘤，在常被误诊为胶质瘤的病变中也可观察到。在非肿瘤性病变中，p53表达不伴有TP53突变，mdm2可能是这些病变中p53表达持续存在的原因。
