Research studies identified novel CDH1 germline variants in women with diagnosed lobular breast cancer (in invasive and/or in situ histotype) and without any family history of gastric carcinoma.
[3][4] In a CDH1 (gene) wild-type situation, lobules are well-organized structures characterized by the cell-cell adhesion mediated through the homophilic binding of E-cadherin molecules on adjacent cells.
In case of a CDH1 (gene) mutation the E-cadherin function can be deregulated, with a decreased cell-cell adhesion and increased cell proliferation, so-called lobular hyperplasia.
Subsequently, in case of a second-hit CDH1 (gene) inactivation, E-cadherin protein expression is undetectable and, consequently, it disrupts the organization of the lobule.
Finally, cancer cells disrupt the basement membrane and invade surrounding breast tissues, a stage that is classified as invasive lobular carcinoma.