RESUMO
BACKGROUND: Invasive lobular breast cancer (ILC) and lobular carcinoma in situ (LCIS) are characterised by loss of E-cadherin expression. However germline CDH1 mutations are rare in cases of ILC with no family history of hereditary diffuse gastric cancer (HDGC) and have not been described in women with LCIS. METHODS: We screened the CDH1 gene in 50 cases of bilateral LCIS/ILC using Sanger sequencing and MLPA. RESULTS: Sanger sequencing revealed four pathogenic germline mutations, including a novel splicing mutation (c.48+1G>A). The remaining three (c.1465insC, c.1942G>T, c.2398delC) have been previously described. All four cases had bilateral LCIS +/- ILC and no family history of gastric cancer. CONCLUSION: CDH1 germline mutations have not been previously described in women with LCIS. We have shown that germline CDH1 mutations are associated with early onset of bilateral LCIS with or without ILC in women without a family history of gastric cancer. CDH1 mutation screening should be considered in women with early onset of bilateral LCIS/ILC with no family history of HDGC.