Abstract
Aims: The roles of tumour suppressor genes: adenomatous polyposis coli (APC) and E‐cadherin (CDH1) were investigated in clear cell renal cell carcinoma.
Methods: Forty‐five human clear cell renal cell carcinomas were tested for APC gene instability by polymerase chain reaction/loss of heterozygosity using the restriction fragment length polymorphism method. E‐cadherin gene was analysed by PCR amplification of tetranucleotide marker (D16S752) and the alleles were visualised by PAGE/silver staining.
Results: The overall proportion of loss of heterozygosity of the APC gene was 37.5% (9/24). D16S752 marker linked to E‐cadherin gene (informativeness 91%) revealed three samples with loss of heterozygosity (7.5%). Interestingly, replication error phenotype was detected in 9.1% of clear cell renal cell carcinoma samples.
Multivariate statistical analysis of samples informative for both APC and E‐cadherin genes showed that, in this data set, loss of heterozygosity of the APC gene is correlated with advanced age and more severe TNM stages. Genetic changes of the E‐cadherin gene, on the other hand, appear to be correlated with younger age groups and less severe TNM stages.
Conclusions: Our results suggest that alterations, both in APC and E‐cadherin genes, are involved in the evolution and progression of clear cell renal cell carcinoma. Microsatellite genetic instability of the E‐cadherin gene indicates that another cellular mechanism, mismatch repair, may also be targeted in this malignancy.