title: Simultaneous bilateral breast carcinomas: a category with frequent coexpression of HER-2 and ER-alpha, high Ki-67 and bcl-2, and low p53.
abstract: The aim of this study was to evaluate clinicopathological characteristics and immunophenotypes of simultaneous bilateral adenocarcinomas of the breast and their axillary metastases. Immunohistochemical analysis and in situ hybridization were performed using formalin-fixed/paraffin-embedded tissues. In total, 15 primary and 9 metastatic tumors from 8 patients were evaluated. The expression of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), Ki 67, p53, bcl-2, and bax were evaluated by immunohistochemistry. Her2 gene amplification was evaluated by chromogenic in situ hybridization (CISH). Four patients were younger that 40 years of age (mean 47 years). Six patients had pleomorphic lobular carcinoma in 1 breast. Four of these had invasive ductal carcinoma in the contralateral breast. One patient had atypical medullary carcinoma in both breasts and 1 patient had atypical medullary carcinoma in 1 breast and pleomorphic lobular carcinoma in the other. The phenotype of the primary tumors and corresponding metastatic tumors was similar for the expression of ER-alpha (p=0.001), PR (p=0.03), and HER-2 (p=0.018). While strong coexpression of HER-2 and ER-alpha is exceptional in hereditary breast carcinoma and sporadic breast carcinoma, 6/8 (75%) patients in this study had tumors with strong coexpression of HER-2 and ER-alpha. P53 protein expression was found in only 2/15 (13%) primary tumors, which is in contrast to BRCA1-related hereditary bilateral breast carcinomas, which often express p53 protein. Most of the patients presented with axillary metastases and had very aggressive course. Characteristically, the tumors showed high levels of expression of ER-alpha and Her2 amplification, were bcl-2 positive, and had high Ki-67 fraction. However, in patients with atypical medullary carcinoma there was no expression of ER-alpha or amplification of Her-2.
authors.affiliation: Department of Pathology, Alexander University Hospital, Medical University, Sofia, Bulgaria.
authors.forename: Assia V
authors.initials: AV
authors.lastname: Bassarova
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.forename: Theophil
authors.initials: T
authors.lastname: Sedloev
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lilleby
authors.forename: Svetlana L
authors.initials: SL
authors.lastname: Hristova
authors.forename: Dimitar Y
authors.initials: DY
authors.lastname: Trifonov
authors.forename: Emina
authors.initials: E
authors.lastname: Torlakovic
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D000328:Adult; D000368:Aged; D001365:Axilla; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009378:Neoplasms, Multiple Primary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53