SIMULTANEOUS LOSS OF E-CADHERIN AND CATENINS IN INVASIVE LOBULAR BREAST-CANCER AND LOBULAR CARCINOMA IN-SITU

Loss of expression of the intercellular adhesion molecule E-cadherin f requently occurs in invasive lobular breast carcinomas as a result of mutational inactivation, Expression patterns of E-cadherin and the mol ecules comprising the cytoplasmic complex of adherens junctions, alpha -, beta- and gamma-catenin, were studied in a series of 38 lobular bre ast carcinomas with known E-cadherin mutation status, The effect of lo ss of E-cadherin by mutational inactivation (or other mechanisms) on t he expression of catenins was investigated, Complete loss of plasma me mbrane-associated E-cadherin expression was observed in 32 out of 38 i nvasive lobular carcinomas, for which in 21 cases a mutation was found in the extracellular domain of E-cadherin. In total, 15 frameshift mu tations of small deletions or insertions, ranging from 1 to 41 bp, thr ee non-sense mutations, and three splice mutations were identified, Mu tations mere scattered over the whole coding region and no hot spots c ould he detected, In all cases, simultaneous loss of E-cadherin and al pha- and beta-catenin expression was found; in 50 per cent of these ca ses, additional loss of gamma-catenin was observed, In six invasive lo bular carcinomas, expression of both E-cadherin and catenins was retai ned, In none of these carcinomas was an E-cadherin mutation detected, Lobular carcinoma in situ adjacent to invasive lobular carcinoma showe d simultaneous loss of E-cadherin and catenins in all the cases studie d-remarkably, also, in four cases positive for E-cadherin and catenin expression in the invasive component, These results indicate that simu ltaneous loss of E-cadherin and alpha-, beta- and gamma-catenin may be an important step in the formation of lobular carcinoma in situ, as a precursor of invasive lobular breast cancer, Events additional to E-c adherin inactivation must be involved in the transition of lobular car cinoma in situ to invasive lobular carcinoma. (C) 1997 John Wiley & So ns, Ltd.