Mitochondrial DNA Content Varies with Pathological Characteristics of Breast Cancer

Abstract

Changes in mitochondrial DNA (mtDNA) content in cancers have been reported with controversial results, probably due to small sample size and variable pathological conditions. In this study, mtDNA content in 302 breast tumor/surrounding normal tissue pairs were evaluated and correlated with the clinico-pathological characteristics of tumors. Overall, mtDNA content in tumor tissues is significantly lower than that in the surrounding normal tissues, P < 0.00001. MtDNA content in tumor tissues decreased with increasing tumor size. However, when the tumor is very large (>50 cm3), mtDNA content started to increase. Similarly, mtDNA content decreased from grades 0 and I to grade II tumors, but increased from grade II to grade III tumors. Tumors with somatic mtDNA alterations in coding region have significantly higher mtDNA content than tumors without somatic mtDNA alterations (P < 0.001). Tumors with somatic mtDNA alterations in the D-Loop region have significantly lower mtDNA content (P < 0.001). Patients with both low and high mtDNA content in tumor tissue have significantly higher hazard of death than patients with median levels of mtDNA content. mtDNA content in tumor tissues change with tumor size, grade, and ER/PR status; significant deviation from the median level of mtDNA content is associated with poor survival.

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

“…These increases were regarded as a compensation process to overcome the oxidative damages from cigarette smoking and to maintain proper mitochondrial function (19). Concerning BIDCs, a decrease in mtDNA copy number was reported in some research articles (37)(38)(39). Nevertheless, we demonstrated a significantly higher mtDNA copy ratio in BIDCs that harbored negative-ER, negative-PR, positive-p53 or high Ki-67 expression.…”

Mitochondrial DNA mutations in human tumor cells

“…Based on this study, it has been deduced that tumor cells do not completely depend on the mitochondria for oxidative phosphorylation to provide energy. Dani et al stated that the higher glycolytic capacity of tumor cells may be due to the increased growth and nutrient demands of tumor cells, which was not against the theory of the importance of oxidative phosphorylation for the survival and growth of tumors (33,34). It was due to the higher nutrient and oxygen demands that numerous tumors continue to grow in vivo via the induction of neovascularization (35).…”

Mitochondrial DNA alteration and pathological progression in colorectal cancer

“…Later in 2009, Fan et al reported that basing on clinical case analysis 82% of malignant breast tumor accompany with lower mtDNA level compared to normal breast tissue [66] . In 2011, the mtDNA content in breast cancer was tested again in 302 cancerous breast tissues and in their corresponding surrounding normal tissues, the result also showed the cancerous tissue contains lower mtDNA content than normal ones [67] .…”