Molecular alterations of E-cadherin gene: Possible role in human bladder carcinogenesis

E-cadherin is a transmembrane glycoprotein which mediates a calcium depende nt homophilic interaction among epithelial cells. The altered expression an d gene mutations of E-cadherin adhesion molecule have been frequently obser ved in various tumors. Several invasive carcinomas showed cell-cell adhesio n loss although the tumor cells expressed considerable amounts of E-cadheri n protein. The purpose of this study was to evaluate the role of E-cadherin gene alterations in genesis and progression of bladder carcinoma by mutati on analysis of coding region, expression analysis and microsatellite instab ility at E-cadherin chromosome locus. We analyzed 30 bladder carcinoma (28 transitional and 2 squamous cell carcinoma) at different stage and grade. T he mutation analysis showed that in one case there was a presence of a poin t mutation at codon 846 that consisted of a G (AGC) to C (ACC) transversion resulting in the replacement of R to T. In another sample the sequence ana lysis revealed a same-sense mutation at the codon 785 (AAC - AAT). The stud y of E-cadherin mRNA by Northern blot analysis showed that there were no di fferences of mRNA levels between tumor and normal mucosa samples. We noted that invasive and anaplastic tumors showed a trend to loss of expression, e ven if we did not find any statistically significant differences. The micro satellite analysis showed the presence of genomic instability in proximity of the E-cadherin gene. Nine out of 30 (30%) specimens presented molecular alterations in at least one out of 2 loci (D16S260 and D16S301) analyzed. T he comparison between microsatellite mutations and clinical-histopathologic al parameters revealed a higher number of alterations in invasive respect t o superficial tumors (p=0.014). On the other hand, there were no statistica l differences regarding the correlation with pathological grade. These obse rvations, which, nevertheless, need to be confirmed in a larger number of p atients, suggest that alterations of E-cadherin gene may be related to path obiology of bladder cancer development and clinical progression.