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 ainino 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.