title: Mitochondrial DNA alterations correlate with the pathological status and the immunological ER, PR, HER-2/neu, p53 and Ki-67 expression in breast invasive ductal carcinoma.
abstract: We analyzed the changes in mitochondrial DNA (mtDNA) copy numbers and the shifting of mtDNA D310 sequence variations (D310 mutation) with their relationships to pathological status and the expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2/neu), tumor-suppressor protein p53 and cellular proliferation protein Ki-67 in breast invasive ductal carcinoma (BIDC), respectively. Fifty-one paraffin-embedded BIDCs and their paired non-cancerous breast tissues were dissected for DNA extraction. The mtDNA copy number and mtDNA D310 sequence variations were determined by quantitative real-time polymerase chain reaction (q-PCR) and PCR-based direct sequencing, respectively. The expression levels of ER, PR, HER-2/neu, p53 and Ki-67 were determined by immunohistochemical (IHC) staining. Compared to the paired non-cancerous breast tissues, 24 (47.1%) BIDCs had elevated mtDNA copy numbers and 29 (56.9%) harbored mtDNA D310 mutations. Advanced T-status (p=0.056), negative-ER (p=0.005), negative-PR (p=0.007), positive-p53 (p=0.050) and higher Ki-67 (p=0.004) expressions were related to a higher mtDNA copy ratio. In addition, advanced T-status (p=0.019) and negative-HER-2/neu expression (p=0.061) were associated with mtDNA D310 mutations. In conclusion, higher mtDNA copy ratio and D310 mutations may be relevant biomarkers correlated with pathological T-status and the expression levels of ER, PR, HER-2/neu, p53 and Ki-67 in BIDCs.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan, R.O.C.
authors.forename: Chen-Sung
authors.initials: CS
authors.lastname: Lin
authors.affiliation: Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei 112, Taiwan, R.O.C.
authors.forename: Shi-Chuan
authors.initials: SC
authors.lastname: Chang
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei 112, Taiwan, R.O.C.
authors.forename: Liang-Hung
authors.initials: LH
authors.lastname: Ou
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Taipei Hospital, Ministry of Health and Welfare, New Taipei City 242, Taiwan, R.O.C.
authors.forename: Chien-Ming
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Department of Pathology, Taipei Hospital, Ministry of Health and Welfare, New Taipei City 242, Taiwan, R.O.C.
authors.forename: Sophie Swen-Wan
authors.initials: SS
authors.lastname: Hsieh
authors.affiliation: Department of Pathology, Taipei Hospital, Ministry of Health and Welfare, New Taipei City 242, Taiwan, R.O.C.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Chung
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei 112, Taiwan, R.O.C.
authors.forename: Kuang-Liang
authors.initials: KL
authors.lastname: King
authors.affiliation: Chon-inn Hospital, Chon-inn Healthcare Corp. Aggregate, New Taipei City 220, Taiwan, R.O.C.
authors.forename: Shoei-Loong
authors.initials: SL
authors.lastname: Lin
authors.affiliation: Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan, R.O.C.
authors.forename: Yau-Huei
authors.initials: YH
authors.lastname: Wei
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D044584:Carcinoma, Ductal / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D056915:DNA Copy Number Variations / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011980:Receptors, Progesterone / Q000096:biosynthesis* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D047628:Estrogen Receptor alpha; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; C508053:ERBB2 protein, human