E-CADHERIN INACTIVATION IN LOBULAR CARCINOMA IN-SITU OF THE BREAST - AN EARLY EVENT IN TUMORIGENESIS

In breast cancer, inactivating point mutations in the E-cadherin gene are frequently found in invasive lobular carcinoma (ILC) but never in invasive ductal carcinoma (IDC). Lobular carcinoma in situ (LCIS) adja cent to ILC has previously been shown to lack E-cadherin expression, b ut whether LCIS without adjacent invasive carcinoma also lacks E-cadhe rin expression and whether the gene mutations present in ILC are alrea dy present in LCIS is not known. We report here that E-cadherin expres sion is absent in six cases of LCIS and present in 150 cases of ductal carcinoma in situ (DCIS), both without an adjacent invasive component . Furthermore, using mutation analysis, we could demonstrate the prese nce of the same truncating mutations and loss of heterozygosity (LOH) of the wild-type E-cadherin in the LCIS component and in the adjacent ILC. Our results indicate that E-cadherin is a very early target gene in lobular breast carcinogenesis and plays a tumour-suppressive role, additional to the previously suggested invasion-suppressive role.