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High mitochondrial content is associated with breast cancer aggressiveness

  • Authors:
    • Patrick Lebok
    • Katharina Schütt
    • Martina Kluth
    • Isabell Witzel
    • Linn Wölber
    • Peter Paluchowski
    • Luigi Terracciano
    • Christian Wilke
    • Uwe Heilenkötter
    • Volkmar Müller
    • Barbara Schmalfeldt
    • Ronald Simon
    • Guido Sauter
    • Ingo Von Leffern
    • Till Krech
    • Rainer Horst Krech
    • Frank Jacobsen
    • Eike Burandt
  • View Affiliations / Copyright

    Affiliations: Institute of Pathology, University Medical Center Hamburg‑Eppendorf, D‑20246 Hamburg, Germany, Department of Gynecology, University Medical Center Hamburg‑Eppendorf, D‑20246 Hamburg, Germany, Department of Gynecology, Regio Clinic Pinneberg, D‑25421 Pinneberg, Germany, Department of Pathology, Basel University Clinics, 4031 Basel, Switzerland, Department of Gynecology, Regio Clinic Elmshorn, D‑25337 Elmshorn, Germany, Department of Gynecology, Clinical Centre Itzehoe, D‑25524 Itzehoe, Germany, Department of Gynecology, Albertinen Clinic Schnelsen, D‑22457 Hamburg, Germany, Institute of Pathology, Clinical Centre Osnabrück, D‑49076 Osnabrück, Germany
    Copyright: © Lebok et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 203
    |
    Published online on: August 8, 2021
       https://doi.org/10.3892/mco.2021.2365
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Abstract

Mitochondria are relevant for cancer initiation 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 immunohistochemical analysis on 2,197 arrayed breast cancer specimens. Results were compared with histological tumor parameters, patient overall survival, tumor cell proliferation using Ki67 labeling index (Ki67LI) and various other molecular features. Tumor cells exhibited stronger MTCO2 expression than normal breast epithelial cells. MTCO2 immunostaining was largely absent in normal breast epithelium, but was observed in 71.9% of 1,797 analyzable cancer specimens, including 34.6% tumors with weak expression, 22.3% with 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, including high Ki67LI, amplifications of HER2, MYC, CCND1 and MDM2, deletions of PTEN, 8p21 and 9p, low estrogen receptor expression (P<0.0001 each) and progesterone receptor expression (P<0.0001). The present study demonstrated that high MTCO2 expression was strongly associated with a poor prognosis and unfavorable phenotypical and molecular tumor features in patients with breast cancer. This suggests that the mitochondrial content may have a pivotal role in breast cancer progression.
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Copy and paste a formatted citation
Spandidos Publications style
Lebok P, Schütt K, Kluth M, Witzel I, Wölber L, Paluchowski P, Terracciano L, Wilke C, Heilenkötter U, Müller V, Müller V, et al: High mitochondrial content is associated with breast cancer aggressiveness. Mol Clin Oncol 15: 203, 2021.
APA
Lebok, P., Schütt, K., Kluth, M., Witzel, I., Wölber, L., Paluchowski, P. ... Burandt, E. (2021). High mitochondrial content is associated with breast cancer aggressiveness. Molecular and Clinical Oncology, 15, 203. https://doi.org/10.3892/mco.2021.2365
MLA
Lebok, P., Schütt, K., Kluth, M., Witzel, I., Wölber, L., Paluchowski, P., Terracciano, L., Wilke, C., Heilenkötter, U., Müller, V., Schmalfeldt, B., Simon, R., Sauter, G., Von Leffern, I., Krech, T., Krech, R. H., Jacobsen, F., Burandt, E."High mitochondrial content is associated with breast cancer aggressiveness". Molecular and Clinical Oncology 15.4 (2021): 203.
Chicago
Lebok, P., Schütt, K., Kluth, M., Witzel, I., Wölber, L., Paluchowski, P., Terracciano, L., Wilke, C., Heilenkötter, U., Müller, V., Schmalfeldt, B., Simon, R., Sauter, G., Von Leffern, I., Krech, T., Krech, R. H., Jacobsen, F., Burandt, E."High mitochondrial content is associated with breast cancer aggressiveness". Molecular and Clinical Oncology 15, no. 4 (2021): 203. https://doi.org/10.3892/mco.2021.2365
Copy and paste a formatted citation
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Spandidos Publications style
Lebok P, Schütt K, Kluth M, Witzel I, Wölber L, Paluchowski P, Terracciano L, Wilke C, Heilenkötter U, Müller V, Müller V, et al: High mitochondrial content is associated with breast cancer aggressiveness. Mol Clin Oncol 15: 203, 2021.
APA
Lebok, P., Schütt, K., Kluth, M., Witzel, I., Wölber, L., Paluchowski, P. ... Burandt, E. (2021). High mitochondrial content is associated with breast cancer aggressiveness. Molecular and Clinical Oncology, 15, 203. https://doi.org/10.3892/mco.2021.2365
MLA
Lebok, P., Schütt, K., Kluth, M., Witzel, I., Wölber, L., Paluchowski, P., Terracciano, L., Wilke, C., Heilenkötter, U., Müller, V., Schmalfeldt, B., Simon, R., Sauter, G., Von Leffern, I., Krech, T., Krech, R. H., Jacobsen, F., Burandt, E."High mitochondrial content is associated with breast cancer aggressiveness". Molecular and Clinical Oncology 15.4 (2021): 203.
Chicago
Lebok, P., Schütt, K., Kluth, M., Witzel, I., Wölber, L., Paluchowski, P., Terracciano, L., Wilke, C., Heilenkötter, U., Müller, V., Schmalfeldt, B., Simon, R., Sauter, G., Von Leffern, I., Krech, T., Krech, R. H., Jacobsen, F., Burandt, E."High mitochondrial content is associated with breast cancer aggressiveness". Molecular and Clinical Oncology 15, no. 4 (2021): 203. https://doi.org/10.3892/mco.2021.2365
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