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

Overview

Journal J Clin Pathol

Specialty Pathology

Date 2004 Dec 30

PMID 15623481

Citations 1

Authors

A Ramburan

F Oladiran

C Smith

G P Hadley

D Govender

Affiliations

Soon will be listed here.

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.

Citing Articles

Genetic clonality is a feature unifying nephroblastomas regardless of the variety of morphological subtypes.

Guertl B, Leuschner I, Harms D, Hoefler G Virchows Arch. 2006; 449(2):171-4.

PMID: 16715229 DOI: 10.1007/s00428-006-0225-2.

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