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

被引:6
作者
Ramburan, A
Oladiran, F
Smith, C
Hadley, GP
Govender, D
机构
[1] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Mol Biol Res Facil, ZA-7925 Durban, South Africa
[2] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Dept Pathol, ZA-7925 Durban, South Africa
[3] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Dept Paediat Surg, ZA-7925 Durban, South Africa
关键词
D O I
10.1136/jcp.2004.019752
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
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页码:44 / 50
页数:7
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