Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinomain situ

作者：Wiljo J. F. de Leeuw, Geert Berx, Carla B. J. Vos, Johannes L. Peterse, Marc J. van de Vijver, Sergey V. Litvinov, Frans M. Van Roy, Cees J. Cornelisse, Anne‐Marie Cleton-Jansen · 发表于：The Journal of Pathology · 年份：1997 · DOI：10.1002/(sici)1096-9896(199712)183:4<404::aid-path1148>3.0.co;2-9 · 被引用次数：310 · 研究领域：Wnt/β-catenin signaling in development and cancer、Cancer-related Molecular Pathways、Cancer-related gene regulation

Loss of expression of the intercellular adhesion molecule E-cadherin frequently occurs in invasive lobular breast carcinomas as a result of mutational inactivation. Expression patterns of E-cadherin and the molecules comprising the cytoplasmic complex of adherens junctions, alpha-, beta- and gamma-catenin, were studied in a series of 38 lobular breast carcinomas with known E-cadherin mutation status. The effect of loss of E-cadherin by mutational inactivation (or other mechanisms) on the expression of catenins was investigated. Complete loss of plasma membrane-associated E-cadherin expression was observed in 32 out of 38 invasive lobular carcinomas, for which in 21 cases a mutation was found in the extracellular domain of E-cadherin. In total, 15 frameshift mutations of small deletions or insertions, ranging from 1 to 41 bp, three non-sense mutations, and three splice mutations were identified. Mutations were scattered over the whole coding region and no hot spots could be detected. In all cases, simultaneous loss of E-cadherin and alpha- and beta-catenin expression was found; in 50 per cent of these cases, additional loss of gamma-catenin was observed. In six invasive lobular carcinomas, expression of both E-cadherin and catenins was retained. In none of these carcinomas was an E-cadherin mutation detected. Lobular carcinoma in situ adjacent to invasive lobular carcinoma showed simultaneous loss of E-cadherin and catenins in all the cases studied--remarkably, also, in four c...