High mitochondrial content is associated with breast cancer aggressiveness

Mitochondria are relevant for cancer i nitia-tion and progression. Antibodies against mitochondrially encoded cytochrome c oxidase II (MTCO2), targeting a mitochondria specific epitope, can be used to quantitate the mitochondria content of tumor cells. The present study evaluated the impact of the cellular mitochondrial content on the prognosis of patients with breast cancer using immu-nohistochemical analysis on 2,197 arrayed breast cancer specimens. Results were compared with histological tumor parameters, patient overal l sur vival, t umor cel l prol i f-eration using Ki67 labeling index (Ki67LI) and various other molecular features. Tumor cells exhibited stronger MTCO2 expression than normal breast epithelial cells. MTCO2 i mmunost aining was largely absent in normal breast epit helium, but was observed i n 71.9% of 1,797 analyzable cancer specimens, including 34.6% tumors with weak expression, 22. 3% wit h moderate expression and 15.0% with strong expression. High MTCO2 expression was significantly associated with advanced tumor stage, high Bloom-Richardson-Elston/Nottingham (BRE) grade, nodal metastasis and shorter overall survival (P<0.0001 each). In multivariate analysis, MTCO2 expression did not provide prognostic information independent of BRE grade, pathological tumor and pathological lymph node status. Additionally, significant associations were observed for high MTCO2 expression and various molecular features, i ncludi ng high Ki67LI, amplifications of HER2, MYC, CCND1 and MDM2, deletions of PTEN, 8p21 and 9p, low estrogen receptor expression (P<0.0001 each) and proges-terone receptor expression (P<0.0001). The present study demonstrated that high MTCO2 expression was strongly associated with a poor prognosis and unfavorable pheno-typical and molecular tumor features in patients with breast cancer. This suggests that the mitochondrial content may have a pivotal role in breast cancer progression.