Gene expression profiling of histologically normal breast tissue in females with human epidermal growth factor receptor 2‑positive breast cancer.
Gene expression profile‑based taxonomy of breast cancer (BC) has been described as a significant breakthrough in comprehending the differences in the origin and behavior of cancer to allow individually tailored therapeutic approaches. In line with this, we hypothesized that the gene expression profile of histologically normal epithelium (HNEpi) could harbor certain genetic abnormalities predisposing breast tissue cells to develop human epidermal growth factor receptor 2 (HER2)‑positive BC. Thus, the aim of the present study was to assess gene expression in normal and BC tissue (BCTis) from patients with BC in order to establish its value as a potential diagnostic marker for cancer development. An array study evaluating a panel of 84 pathway‑ and disease‑specific genes in HER2‑positive BC and tumor‑adjacent HNEpi was performed using quantitative polymerase chain reaction in 12 patients using microdissected samples from frozen tissue. Common prognostic and predictive parameters of BC were assessed by immunohistochemistry and in situ hybridization. In the BCTis and HNEpi samples of 12 HER2‑positive subjects with BC, the expression of 2,016 genes was assessed. A total of 39.3% of genes were deregulated at a minimal two‑fold deregulation rate and 10.7% at a five‑fold deregulation rate in samples of HNEpi or BCTis. Significant differences in gene expression between BCTis and HNEpi samples were revealed for BCL2L2, CD44, CTSD, EGFR, ERBB2, ITGA6, NGFB, RPL27, SCBG2A1 and SCGB1D2 genes (P<0.05), as well as GSN, KIT, KLK5, SERPINB5 and STC2 genes (P<0.01). Insignificant differences (P<0.07) were observed for CCNA1, CLU, DLC1, GABRP and IL6 genes. The ontological gene analyses revealed that the majority of the deregulated genes in the HNEpi samples were part of the functional gene group directly associated with BC origin and prognosis. Functional analysis showed that the most frequent gene deregulations occurred in genes associated with apoptosis and cell cycle regulation in BCTis samples, and with angiogenesis, regulation of the cell cycle and transcriptional activity in HNEpi samples. The molecular profiling of HNEpi breast tissue revealed gene expression abnormalities that may represent potential markers of increased risk for HER2‑positive malignant transformation of breast tissue, and may be able to be employed as predictors of prognosis.
Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Bratislava, Martin 036 01, Slovak Republic.
Pavol
P
Zubor
Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Bratislava, Martin 036 01, Slovak Republic.
Jozef
J
Hatok
Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Bratislava, Martin 036 01, Slovak Republic.
Petra
P
Moricova
Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Bratislava, Martin 036 01, Slovak Republic.
Ivana
I
Kapustova
Department of Pathology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Bratislava, Martin 036 01, Slovak Republic.
Karol
K
Kajo
Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Bratislava, Martin 036 01, Slovak Republic.
Andrea
A
Mendelova
Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Bratislava, Martin 036 01, Slovak Republic.
Monika Kmetova
MK
Sivonova
Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Bratislava, Martin 036 01, Slovak Republic.
Jan
J
Danko
D014408:Biomarkers, Tumor / Q000378:metabolism; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D059467:Transcriptome
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human