title: Correlation between ER, PR, HER-2, Bcl-2, p53, proliferative and apoptotic indexes with HER-2 gene amplification and TOP2A gene amplification and deletion in four molecular subtypes of breast cancer.
abstract: The aim of our study was to investigate HER-2 and TOP2A gene status and their correlation with Bcl-2, p53, Ki67, ssDNA, and clinicopathological parameters in four molecular subtypes of breast cancer. Seventy-four paraffin-embedded samples are immunohistochemically studied for the expression of estrogen receptor (ER), progesterone receptor (PR), HER-2, p53, Bcl-2, ssDNA, and Ki67, while HER-2 and TOP2A gene status by fluorescence in situ hybridization was investigated in 60 samples. Luminal A and B subtypes were characterized with small tumor size, intermediate histological grade, negative lymph node, and metastatic status, while triple negative and HER-2 positive subtypes were associated with larger tumor size, poorly differentiated tumors, and positive lymph node status. p53, Ki67, and ssDNA expression was higher in triple negative and HER-2 positive than in luminal subtypes, while ER, PR, and Bcl-2 dominated in luminal subtypes. HER-2 gene status was higher in luminal B and HER-2 positive than in luminal A and triple negative subtypes, while TOP2A gene status was similar. HER-2 gene status positively correlated with TOP2A gene status, HER-2 receptor, and histological grade, while negative correlation characterized relationship between HER-2 gene status and ER, PR, and Bcl-2. The shortened overall survival period characterized patients from triple negative breast cancer subtype (18.7 months). HER-2 and TOP2A gene amplification showed a tendency to be associated with larger tumor size, positive lymph node status, high level of apoptotic and proliferative indexes, and low level of p53 and Bcl-2 expression, which all together indicate group of patients with similar outcome during the progression of the disease.
authors.affiliation: Institute for Medical Research, University of Belgrade, Dr Subotića 4, PO Box 39, 11129, Belgrade 102, Serbia, oliveram@imi.bg.ac.rs.
authors.forename: Olivera
authors.initials: O
authors.lastname: Mitrović
authors.forename: Vladan
authors.initials: V
authors.lastname: Čokić
authors.forename: Dragoslava
authors.initials: D
authors.lastname: Đikić
authors.forename: Mirela
authors.initials: M
authors.lastname: Budeč
authors.forename: Sanja
authors.initials: S
authors.lastname: Vignjević
authors.forename: Tijana
authors.initials: T
authors.lastname: Subotički
authors.forename: Maja
authors.initials: M
authors.lastname: Gulan
authors.forename: Snežana
authors.initials: S
authors.lastname: Radović
authors.forename: Snežana
authors.initials: S
authors.lastname: Furtula
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000075223:Poly-ADP-Ribose Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D000075223:Poly-ADP-Ribose Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; C000595707:BCL2 protein, human; C506487:ESR1 protein, human; C495901:TP53 protein, human; C508053:ERBB2 protein, human; C000618811:TOP2A protein, human