title: Are synchronous and metachronous bilateral breast cancers different? An immunohistochemical analysis aimed at intrinsic tumor phenotype.
abstract: The biology and pathomechanism of bilateral breast cancers is not fully understood. We compared the morphological and immunohistochemical characteristics of primary tumors in patients with synchronous bilateral breast cancers and metachronous bilateral breast cancers, with special focus on intrinsic tumor phenotype.
  
  
  METHODS
  Tumor morphology and expression of 8 immunohistochemical markers were assessed in tissue microarrays containing primary breast tumor cores from 113 metachronous bilateral breast cancers and 61 synchronous bilateral breast cancers. Analyzed markers included hormone receptors (estrogen receptor, progesterone receptor), HER2, Ki67, cytokeratin 5/6, E-cadherin, vimentin and epidermal growth factor receptor. Cutoff levels are provided in the table.
  
  
  RESULTS
  Metachronous bilateral breast cancers tumors had lower estrogen receptor expression (p=0.047) and higher expression of cytokeratin 5/6 (p=0.017) and of vimentin (p=0.008); in multivariate analysis only vimentin retained the significance (p=0.01). Ten (13%) and 11 (26%) of metachronous bilateral breast cancers and synchronous bilateral breast cancers had luminal A phenotype, 39 (50%) and 15 (36%) were luminal B HER2-negative, 13 (17%) and 12 (28%) - luminal B HER2-positive, 3 (4%) and 2 (5%) - HER2-positive (not luminal), and 12 (16%) and 2 (5%) had triple negative phenotype (p=0.07).
  
  
  CONCLUSIONS
  Metachronous bilateral breast cancers, compared to synchronous bilateral breast cancers, are characterized by more aggressive phenotype, expressed by lower expression of estrogen receptor and stronger expression of cytokeratin 5/6 and vimentin; this does not, however, translate into differences in the distribution of intrinsic tumor phenotypes.
authors.affiliation: Department of Oncology and Radiotherapy, Medical University of Gdańsk Gdańsk, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Senkus
authors.affiliation: Department of Pathomorphology, Medical University of Gdańsk Gdańsk, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Szade
authors.affiliation: Department of Pathomorphology, Medical University of Gdańsk Gdańsk, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Pieczyńska
authors.affiliation: Laboratory of Cell Biology, Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk Gdańsk, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Zaczek
authors.affiliation: Regional Oncology Center Gdańsk, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Pikiel
authors.affiliation: Regional Oncology Center Gdańsk, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Sosińska-Mielcarek
authors.affiliation: West-Pomeranian Oncology Center Szczecin, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Karpińska
authors.affiliation: Department of Oncology and Radiotherapy, Medical University of Gdańsk Gdańsk, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007150:Immunohistochemistry; D009378:Neoplasms, Multiple Primary / Q000378:metabolism* / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor
keywords: Bilateral breast cancer; immunohistochemistry; intrinsic phenotype; metachronous; synchronous