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

作者：Lin Chen Sung; Chang Shi Chuan; Ou Liang Hung; Chen Chien Ming; Hsieh Sophie Swen Wan; Chung Yu Ping; King Kuang Liang; Lin Shoei Loong^*; Wei Yau Huei

来源：Oncology Reports, 2015, 33(6): 2924-2934.

DOI：10.3892/or.2015.3887

• breast invasive ductal carcinoma
• mitochondrial DNA copy number
• D310 mutation
• estrogen receptor
• HER-2/neu
• protein Ki-67
• protein p53
• progesterone receptor

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.

• 出版日期2015-6