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Aims—The relation between lobular carcinoma in situ (LCIS) and invasive breast cancer is unresolved. In an attempt to establish whether LCIS is a precursor of invasive cancer the mutational status and the expression of E-cadherin was analysed in LCIS and associated invasive breast carcinoma in 23 patients. Methods—Foci of LCIS and associated invasive carcinoma were individually microdissected from tissue from 23 patients. Exons 4–16 of the E-cadherin gene were analysed using single strand conformation polymorphism (SSCP); protein expression and the localisation of E-cadherin and β-catenin were assessed with the use of immunohistochemistry. Results—Immunohistochemistry revealed a lack of expression of E-cadherin and β-catenin in most LCIS samples and invasive foci. In all but four cases, the staining pattern was identical in the LCIS and associated invasive areas. When E-cadherin was absent, β-catenin was also undetected, suggesting a lack of expression of alternative classic cadherin members in these lesions. Coincident E-cadherin mutations in LCIS and associated invasive carcinoma were not identified in this series of patients. However, mutational analysis of E-cadherin in multiple foci of carcinoma in situ surrounding an invasive lesion provided evidence to support ductal carcinoma in situ as a precursor of invasive ductal carcinoma. Conclusion—These data support the hypothesis that LCIS is not a precursor of invasive breast carcinoma but a marker of increased risk of developing invasive disease.

Dental enamel development occurs in stages as observed by the changing morphology of the ameloblasts that are responsible for enamel formation. During the secretory stage of development, proteins including MMP20 are secreted into the enamel matrix. MMP20 is required for proper enamel formation as mutation of the Mmp20 gene causes autosomal recessive amelogenesis imperfecta. Here, we examined in detail the morphology of the Mmp20-null ameloblast cell layer. Intriguingly, we found that the Mmp20-null mouse secretory stage ameloblasts retract their Tomes’ processes as if preparing to enter the maturation stage but later reextend their Tomes’ processes as if resuming the secretory stage. We also demonstrated that MMP20 cleaves epithelial cadherin, i.e. E-cadherin. Cadherins are transmembrane proteins with extracellular domains that provide adhesive contacts between neighboring cells. Their intracellular domains bind to the cell cytoskeleton through catenins, including β-catenin. When specific MMPs cleave the cadherin extracellular domain, β-catenin is released and may locate to the cell nucleus as a transcription factor. Therefore, MMP20 may influence ameloblast developmental progression through hydrolysis of cadherin extracellular domains with associated release of transcription factor(s).