E-CADHERIN IS A TUMOR INVASION SUPPRESSOR GENE MUTATED IN HUMAN LOBULAR BREAST CANCERS

Compelling experimental evidence exists for a potent invasion suppress or role of the cell-cell adhesion molecule E-cadherin. In addition, a tumour suppressor effect has been suggested for E-cadherin. In human c ancers, partial or complete loss of E-cadherin expression correlates w ith malignancy. To investigate the molecular basis for this altered ex pression we developed a comprehensive PCR/SSCP mutation screen for the human E-cadherin gene, For 49 breast cancer patients the occurrence o f tumour-specific mutations in the E-cadherin gene was examined. No re levant DNA changes were encountered in any of 42 infiltrative ductal o r medullary breast carcinoma samples, In contrast, four out of seven i nfiltrative lobular breast carcinomas harboured protein truncation mut ations (three nonsense and one frameshift) in the extracellular part o f the E-cadherin protein. Each of the four lobular carcinomas with E-c adherin mutations showed tumour-specific loss of heterozygosity of chr omosomal region 16q22.1 containing the E-cadherin locus. In compliance with this, no E-cadherin expression was detectable by immunohistochem istry in these four tumours. These findings offer a molecular explanat ion for the typical scattered tumour cell growth in infiltrative lobul ar breast cancer.