title: Pleomorphic lobular carcinoma of the breast: role of comprehensive molecular pathology in characterization of an entity.
abstract: Immunohistochemical analysis of E-cadherin has changed the way lobular neoplasia is perceived. It has helped to classify difficult cases of carcinoma in situ with indeterminate features and led to the identification of new variants of lobular carcinoma. Pleomorphic lobular carcinoma (PLC) and pleomorphic lobular carcinoma in situ (PLCIS), recently described variants of invasive and in situ classic lobular carcinoma, are reported to be associated with more aggressive clinical behaviour. Although PLC/PLCIS show morphological features of classic lobular neoplasia and lack E-cadherin expression, it is still unclear whether these lesions evolve through the same genetic pathway as lobular carcinomas or are high-grade ductal neoplasms that have lost E-cadherin. Here we have analysed a case of extensive PLCIS and invasive PLC associated with areas of E-cadherin-negative carcinoma in situ with indeterminate features, using immunohistochemistry, chromogenic in situ hybridization, high-resolution comparative genomic hybridization (CGH) and array-based CGH. We observed that all lesions lacked E-cadherin and beta-catenin and showed gain of 1q and loss of 16q, features that are typical of lobular carcinomas but are not seen in high-grade ductal lesions. In addition, amplifications of c-myc and HER2 were detected in the pleomorphic components, which may account for the high-grade features in this case and the reported aggressive clinical behaviour of these lesions. Taken together, these data suggest that at least some PLCs may evolve from the same precursor or through the same genetic pathway as classic lobular carcinomas.
authors.affiliation: The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London SW3 6JB, UK. jorgerf@icr.ac.uk
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.forename: Pete T
authors.initials: PT
authors.lastname: Simpson
authors.forename: Chris
authors.initials: C
authors.lastname: Jones
authors.forename: Dawn
authors.initials: D
authors.lastname: Steele
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay
authors.forename: Marjan
authors.initials: M
authors.lastname: Iravani
authors.forename: Kerry
authors.initials: K
authors.lastname: Fenwick
authors.forename: Haukur
authors.initials: H
authors.lastname: Valgeirsson
authors.forename: Maryou
authors.initials: M
authors.lastname: Lambros
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
authors.forename: Jose
authors.initials: J
authors.lastname: Palacios
authors.forename: Fernando
authors.initials: F
authors.lastname: Schmitt
authors.forename: Sunil R
authors.initials: SR
authors.lastname: Lakhani
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D002278:Carcinoma in Situ / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002869:Chromosome Aberrations; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization / Q000379:methods; D042282:Microdissection / Q000379:methods; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin