Genetic changes of the E-cadherin and APC tumour suppressor genes in clear cell renal cell carcinoma

• Published in: Pathology 2004-04, Vol.36 (2), p.145-151
• Main Authors: PECINA-SLAUS, Nives, GALL-TROSELJ, Koraljka, SLAUS, Mario, RADIC, Kresimir, NIKUSEVA-MARTIC, Tamara, PAVELIC, Kresimir
• Format: Article
• Language: English
• Subjects: Adenocarcinoma, Clear Cell - genetics; Adenocarcinoma, Clear Cell - metabolism; Adenocarcinoma, Clear Cell - pathology; Adenomatous polyposis coli gene; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Cadherins - genetics; Cadherins - metabolism; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - pathology; CDH1 gene; clear cell renal cell carcinoma; DNA, Neoplasm - analysis; Electrophoresis, Gel, Two-Dimensional; Female; Gastroenterology. Liver. Pancreas. Abdomen; General aspects; Genes, APC; Humans; Kidney Neoplasms - genetics; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Kidneys; Loss of Heterozygosity; Male; Medical sciences; Middle Aged; Multivariate Analysis; Neoplasm Staging; Nephrology. Urinary tract diseases; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; replication error; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Tumors of the urinary system
• ISSN: 0031-3025; 1465-3931
• DOI: 10.1080/00313020410001671984

The roles of tumour suppressor genes: adenomatous polyposis coli (APC) and E-cadherin (CDH1) were investigated in clear cell renal cell carcinoma. 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. 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. 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.