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Mixed ductal-lobular carcinomas: evidence for progression from ductal to lobular morphology.
McCart Reed, Amy E; Kutasovic, Jamie R; Nones, Katia; Saunus, Jodi M; Da Silva, Leonard; Newell, Felicity; Kazakoff, Stephen; Melville, Lewis; Jayanthan, Janani; Vargas, Ana Cristina; Reid, Lynne E; Beesley, Jonathan; Chen, Xiao Qing; Patch, Anne-Marie; Clouston, David; Porter, Alan; Evans, Elizabeth; Pearson, John V; Chenevix-Trench, Georgia; Cummings, Margaret C; Waddell, Nicola; Lakhani, Sunil R; Simpson, Peter T.
Afiliação
  • McCart Reed AE; Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
  • Kutasovic JR; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Nones K; Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
  • Saunus JM; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Da Silva L; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Newell F; Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
  • Kazakoff S; Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
  • Melville L; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Jayanthan J; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Vargas AC; Pathology Queensland, The Royal Brisbane and Women's Hospital, Brisbane, Australia.
  • Reid LE; Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
  • Beesley J; Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
  • Chen XQ; Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
  • Patch AM; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Clouston D; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Porter A; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Evans E; TissuPath, Mt Waverley, Melbourne, Australia.
  • Pearson JV; The Wesley Breast Clinic, The Wesley Hospital, Brisbane, Australia.
  • Chenevix-Trench G; The Wesley Breast Clinic, The Wesley Hospital, Brisbane, Australia.
  • Cummings MC; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Waddell N; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Lakhani SR; Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
  • Simpson PT; Pathology Queensland, The Royal Brisbane and Women's Hospital, Brisbane, Australia.
J Pathol ; 244(4): 460-468, 2018 04.
Article em En | MEDLINE | ID: mdl-29344954
Mixed ductal-lobular carcinomas (MDLs) show both ductal and lobular morphology, and constitute an archetypal example of intratumoural morphological heterogeneity. The mechanisms underlying the coexistence of these different morphological entities are poorly understood, although theories include that these components either represent 'collision' of independent tumours or evolve from a common ancestor. We performed comprehensive clinicopathological analysis of a cohort of 82 MDLs, and found that: (1) MDLs more frequently coexist with ductal carcinoma in situ (DCIS) than with lobular carcinoma in situ (LCIS); (2) the E-cadherin-catenin complex was normal in the ductal component in 77.6% of tumours; and (3) in the lobular component, E-cadherin was almost always aberrantly located in the cytoplasm, in contrast to invasive lobular carcinoma (ILC), where E-cadherin is typically absent. Comparative genomic hybridization and multiregion whole exome sequencing of four representative cases revealed that all morphologically distinct components within an individual case were clonally related. The mutations identified varied between cases; those associated with a common clonal ancestry included BRCA2, TBX3, and TP53, whereas those associated with clonal divergence included CDH1 and ESR1. Together, these data support a model in which separate morphological components of MDLs arise from a common ancestor, and lobular morphology can arise via a ductal pathway of tumour progression. In MDLs that present with LCIS and DCIS, the clonal divergence probably occurs early, and is frequently associated with complete loss of E-cadherin expression, as in ILC, whereas, in the majority of MDLs, which present with DCIS but not LCIS, direct clonal divergence from the ductal to the lobular phenotype occurs late in tumour evolution, and is associated with aberrant expression of E-cadherin. The mechanisms driving the phenotypic change may involve E-cadherin-catenin complex deregulation, but are yet to be fully elucidated, as there is significant intertumoural heterogeneity, and each case may have a unique molecular mechanism. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Neoplasias Complexas Mistas / Carcinoma Intraductal não Infiltrante / Carcinoma de Mama in situ Limite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: J Pathol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Austrália

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Neoplasias Complexas Mistas / Carcinoma Intraductal não Infiltrante / Carcinoma de Mama in situ Limite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: J Pathol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Austrália