Beniers A J, Efferth T, Füzesi L, Granzen B, Mertens R, Jakse G
Institute of Applied Biomedical Research, NL-6278 NA Gulpen-Wittem, The Netherlands.
Int J Oncol. 2001 Jan;18(1):133-9.
Although a correlation between anaplasia and mutations of the p53 tumor suppressor gene has been found in Wilms' tumor (WT) a prognostic significance of p53 in WT remains largely unresolved. The goal of this study was to obtain a better understanding of the role of p53 expression in WT. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded tumor tissues from 21 patients treated in our clinic between 1984 and 1996. Eight patients presented with stage I, six with stage II, two with stage III, four with stage IV and one patient with stage V disease. According to the presence of anaplasia, four cases were categorized as of unfavorable histology based on the criteria of the National Wilms' Tumor Study Group. Seven out of 21 WTs were positive for p53. One out of the eight patients with stage I and one out of the six patients with stage II disease scored positive for p53 as were 2/2 patients with stage III and 3/4 patients with stage IV disease. Four tumors scored positive for anaplasia (one stage I, one stage II and two stage IV disease) and all four belonged to the p53 positive group. Three of these patients died of progressive disease. Immunopositivity in general was focal in the blastemal and epithelial parts of the tumors, with differences in intensity of staining ranging from moderate to strong. Positivity in the stromal components was restricted to single cells. Statistical analysis revealed significant correlations of p53 expression to anaplasia and to survival, respectively. The association of p53 expression to tumor stage was of borderline significance. To support immunohistochemistry, we performed PCR/SSCP and DNA sequence analyses on two cases, one whose immunopositivity suggested a mutated p53, and another case which was immunonegative. A CGG --> TGG base change in codon 282 of exon 8 was found in the immunopositive tumor. In conclusion, p53 may be of prognostic relevance for poor outcome being present in close association with unfavorable histology of WTs.
虽然在肾母细胞瘤（WT）中已发现间变与p53肿瘤抑制基因突变之间存在关联，但p53在WT中的预后意义仍未完全明确。本研究的目的是更好地了解p53表达在WT中的作用。对1984年至1996年间在我们诊所接受治疗的21例患者的福尔马林固定石蜡包埋肿瘤组织进行了免疫组织化学分析。8例患者为I期，6例为II期，2例为III期，4例为IV期，1例为V期疾病。根据间变的存在情况，根据国家肾母细胞瘤研究组的标准，4例病例被归类为组织学不良。21例WT中有7例p53呈阳性。I期的8例患者中有1例、II期的6例患者中有1例p53评分呈阳性，III期的2/2例患者和IV期的3/4例患者也是如此。4个肿瘤间变呈阳性（1例I期、1例II期和2例IV期疾病），且这4个肿瘤均属于p53阳性组。这些患者中有3例死于疾病进展。一般来说，免疫阳性在肿瘤的胚芽和上皮部分呈局灶性，染色强度差异从中度到强。基质成分中的阳性仅限于单个细胞。统计分析显示p53表达分别与间变和生存存在显著相关性。p53表达与肿瘤分期的关联具有临界显著性。为了支持免疫组织化学，我们对2例病例进行了PCR/SSCP和DNA序列分析，1例免疫阳性提示p53突变，另1例免疫阴性。在免疫阳性肿瘤中发现外显子8的第282密码子发生了CGG→TGG碱基变化。总之，p53可能与预后不良相关，与WT的不良组织学密切相关。
