Point mutation of the E-cadherin gene in invasive lobular carcinoma of the breast.

Reduced or heterogeneous expression of E-cadherin has been demonstrated immunohistochemically in poorly differentiated carcinoma, which frequently shows weak intercellular adhesiveness and marked invasiveness. In vitro, not only reduced expression but also structural abnormalities of E-cadherin have been observed in human carcinoma cell lines which grow in a loosely adhering manner. To clarify the participation of structural abnormalities of E-cadherin in cancer invasion in vivo, sequence abnormalities were examined in the cadherin domain (exons 5, 6, 7 and 8) including the region essential for E-cadherin specific binding, using the polymerase chain reaction-single-strand conformation polymorphism method and direct sequencing in invasive lobular carcinoma of the breast, in which cancer cells become detached from each other and invade the stroma in a particularly scattered pattern. In 2 (10%) of the 20 cases examined, an identical sequence abnormality was detected in E-cadherin exon 7, i.e. a point mutation of codon 315 (AAT to AGT) which resulted in a single amino acid substitution (asparagine to serine). This mutation may abolish the E-cadherin-mediated cell-cell adhesion and be at least partly responsible for the weak intercellular adhesiveness and scattered histological pattern of the tumor.