12th Ljudevit Jurak International Symposium on
Comparative Pathology
Zagreb
June 1-2, 2001

ABSTRACT
GENETIC INSTABILITIES OF THE E-CADHERIN GENE (CHH1) IN RENAL CELL CARCINOMA
N. Peæina-Šlaus, K. Gall-Trošelj*, K. Radiæ**, K. Paveliæ*,
J. Paveliæ*
Department of Biology, School of Medicine, University of Zagreb, Croatia
*Division of Molecular Medicine, Ruðer Boškoviæ Institute, Zagreb, Croatia
**School of Medicine, University of Zagreb, Zagreb, Croatia
E-cadherin is one of the most important molecules of cell-cell adhesion in epithelial tissues, generally localized on the surfaces of epithelial cells in a region of cell-cell contact that is known as the adherens junction. In our study the role of the tumor suppressor gene E-cadherin (CDH1) was investigated in renal cell carcinoma (RCC). Our previous study showed that the APC tumor suppressor gene is involved in renal carcinogenesis, demonstrating indirectly that cell-cell interaction is one of the targets involved in renal cell carcinoma progression. Since E-cadherin is bound to the APC gene via beta-catenin, we were interested to see any detection of E-cadherins involvement in RCC.
Forty-five human renal cell carcinomas together with autologous peripheral blood samples were tested for gene instability. Using specific oligonucleotide primers E-cadherin gene was analyzed by PCR amplification of the tetranucleotide repeat polymorphic marker (D16S752) and the alleles were visualized by PAGE/silver staining.
The polymorphic marker for E-cadherin gene was highly informative (39/43, 91%). Our results demonstrate that from 39 informative tumor samples 2  (5%) demonstrated LOH.
Interestingly, in another three RCC samples we detected another type of genomic instability; replication error (RER+). Both samples which showed LOH of the E-cadherin had also LOH of the APC gene, while only one RER+ sample of the E-cadherin gene showed LOH at the APC locus. The overall number of genetic instabilities in our sample was 5/39 (13%).
Pathohistological diagnosis showed no correlation with molecular data. Our results suggest that alterations in E-cadherin gene are involved in the evolution and progression of RCC. Microsatellite genetic instability of the E-cadherin gene indicates that another cellular mechanism, mismatch repair, is targeted in RCC.
Program