肾母细胞瘤中腺瘤性结肠息肉病（APC）基因的微卫星分析及β连环蛋白的免疫表达：一项纳入83例接受术前化疗患者的研究

Microsatellite analysis of the adenomatous polyposis coli (APC) gene and immunoexpression of beta catenin in nephroblastoma: a study including 83 cases treated with preoperative chemotherapy.

作者信息

Ramburan A, Oladiran F, Smith C, Hadley G P, Govender D

机构信息

Molecular Biology Research Facility, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Congella, 7925 Durban, South Africa.

出版信息

J Clin Pathol. 2005 Jan;58(1):44-50. doi: 10.1136/jcp.2004.019752.

DOI:10.1136/jcp.2004.019752

PMID:15623481

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1770552/

Abstract

AIMS

To determine whether microsatellite mutations of the adenomatous polyposis coli (APC) gene have pathological or prognostic significance in nephroblastomas and to correlate APC alterations with beta catenin immunoexpression.

METHODS

One hundred nephroblastomas were analysed, 83 of which received preoperative chemotherapy. Normal and tumour DNA was isolated using standard proteinase K digestion and phenol/chloroform extraction from paraffin wax embedded tissue. Polymerase chain reaction using four APC microsatellite markers-D5S210, D5S299, D5S82, and D5S346-was performed and the products analysed. Immunohistochemistry was performed using the LSAB kit with diaminobenzidine as chromogen. Results were correlated with clinicopathological data using the chi(2) test.

RESULTS

Allelic imbalance/loss of heterozygosity was more frequent than microsatellite instability, with 30% of cases showing allelic imbalance/ loss of heterozygosity and 16% showing microsatellite instability. Although there was a significant correlation between the results for individual markers and the clinicopathological data, the overall results do not support a prognostic role for APC in nephroblastoma. Expression of beta catenin was seen in 93% of cases. Staining was predominantly membranous, with epithelium, blastema, and stroma being immunoreactive. Cytoplasmic redistribution was seen in 58% of cases, but no nuclear staining was detected. No significant associations between beta catenin expression and the clinicopathological parameters were found. Kaplan-Meier survival plots showed that patients with loss of membranous staining and pronounced cytoplasmic staining (score, 3) had a significantly shorter survival (p = 0.04; median survival, 5.87 months).

CONCLUSION

Microsatellite analysis of APC and immunoexpression of beta catenin did not provide significant pathological or prognostic information in this cohort of nephroblastomas.

摘要

目的

确定腺瘤性息肉病 coli（APC）基因的微卫星突变在肾母细胞瘤中是否具有病理或预后意义，并将 APC 改变与β连环蛋白免疫表达相关联。

方法

分析了 100 例肾母细胞瘤，其中 83 例接受了术前化疗。使用标准蛋白酶 K 消化和苯酚/氯仿提取法从石蜡包埋组织中分离正常和肿瘤 DNA。使用四个 APC 微卫星标记物——D5S210、D5S299、D5S82 和 D5S346 进行聚合酶链反应，并对产物进行分析。使用以二氨基联苯胺为显色剂的 LSAB 试剂盒进行免疫组织化学。使用卡方检验将结果与临床病理数据相关联。

结果

等位基因失衡/杂合性缺失比微卫星不稳定性更常见，30%的病例显示等位基因失衡/杂合性缺失，16%显示微卫星不稳定性。尽管个别标记物的结果与临床病理数据之间存在显著相关性，但总体结果不支持 APC 在肾母细胞瘤中的预后作用。93%的病例中可见β连环蛋白表达。染色主要为膜性，上皮、胚基和间质具有免疫反应性。58%的病例中可见细胞质重新分布，但未检测到核染色。未发现β连环蛋白表达与临床病理参数之间存在显著关联。Kaplan-Meier 生存曲线显示，膜性染色缺失且细胞质染色明显（评分，3）的患者生存期明显较短（p = 0.04；中位生存期，5.87 个月）。