Park W S, Oh R R, Park J Y, Kim P J, Shin M S, Lee J H, Kim H S, Lee S H, Kim S Y, Park Y G, An W G, Kim H S, Jang J J, Yoo N J, Lee J Y
Department of Pathology and Cancer Research Institute, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Sacho-gu, Seoul 137-701, Korea.
J Pathol. 2001 Apr;193(4):483-90. doi: 10.1002/1096-9896(2000)9999:9999<::aid-path804>3.0.co;2-r.
In this study, mutational and immunohistochemical analyses of beta-catenin were performed in 30 hepatoblastomas, to assess the prevalence of alterations of the Wnt pathway with respect to clinicopathological parameters and survival. Four missense mutations of beta-catenin (13.3%) were detected and there was strong immunoreactivity for beta-catenin in the cytoplasm and/or the nucleus in 97% of hepatoblastomas. Nuclear and cytoplasmic staining was demonstrated in 19 of 30 tumours (63%), while ten revealed only cytoplasmic staining. Statistically, this nuclear beta-catenin staining was significantly higher in the embryonal (Fisher exact test; p=0.00393) or undifferentiated type (p=0.00156) of hepatoblastoma than in the fetal type, but there was no difference between clinical stages I and II and clinical stages III and IV (p=0.175). Cumulative survival curves showed that nuclear beta-catenin staining (generalized Wilcoxon test; p=0.0088), undifferentiated histological type (p=0.0305), and clinical stages III and IV (p=0.0107) were significantly correlated with shorter survival time in these patients. Moreover, Cox multivariate analysis provides evidence that nuclear beta-catenin staining is the most important prognostic factor for survival (p=0.0090). It is therefore concluded that immunohistochemical analysis of beta-catenin might be a useful clinical tool for estimating the prognosis for patients with hepatoblastoma.
在本研究中,对30例肝母细胞瘤进行了β-连环蛋白的突变和免疫组化分析,以评估Wnt信号通路改变与临床病理参数及生存率的相关性。检测到4例β-连环蛋白错义突变(13.3%),97%的肝母细胞瘤在细胞质和/或细胞核中β-连环蛋白呈强免疫反应性。30例肿瘤中有19例(63%)表现为细胞核和细胞质染色,10例仅表现为细胞质染色。统计学分析显示,胚胎型(Fisher精确检验;p = 0.00393)或未分化型(p = 0.00156)肝母细胞瘤的细胞核β-连环蛋白染色显著高于胎儿型,但临床I期和II期与临床III期和IV期之间无差异(p = 0.175)。累积生存曲线显示,细胞核β-连环蛋白染色(广义Wilcoxon检验;p = 0.0088)、未分化组织学类型(p = 0.0305)以及临床III期和IV期(p = 0.0107)与这些患者较短的生存时间显著相关。此外,Cox多因素分析表明细胞核β-连环蛋白染色是生存的最重要预后因素(p = 0.0090)。因此得出结论,β-连环蛋白的免疫组化分析可能是评估肝母细胞瘤患者预后的一种有用的临床工具。