Lobular carcinoma in situ of the breast is not caused by constitutional mutations in the E-cadherin gene

Lobular carcinoma in situ (LCIS) is an unusual histological pattern of non- invasive neoplastic disease of the breast occurring predominantly in women aged between 40 and 50 years. LCIS is frequently multicentric and bilateral , and there is evidence that it is associated with an elevated familial ris k or breast cancer. Although women with LCIS suffer an increased risk of in vasive breast disease, this risk is moderate suggesting that LCIS may resul t from mutation of a gene or genes conferring a high risk of LCIS, but a lo wer risk of invasive breast cancer. The high frequency of somatic mutations in E-cadherin in LCIS, coupled with recent reports that germline mutations in this gene can predispose to diffuse gastric cancer, raised the possibil ity that constitutional E-cadherin mutations may confer susceptibility to L CIS. In order to explore this possibility we have examined a series of 65 L CIS patients for germline E-cadherin mutations. Four polymorphisms were det ected but no pathogenic mutations were identified. The results indicate tha t E-cadherin is unlikely to act as a susceptibility gene for LCIS. (C) 2000 Cancer Research Campaign.