High mitochondrial content is associated with breast cancer aggressiveness
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High mitochondrial content is associated with breast cancer aggressiveness. / Lebok, Patrick; Schütt, Katharina; Kluth, Martina; Witzel, Isabell; Wölber, Linn; Paluchowski, Peter; Terracciano, Luigi; Wilke, Christian; Heilenkötter, Uwe; Müller, Volkmar; Schmalfeldt, Barbara; Simon, Ronald; Sauter, Guido; Von Leffern, Ingo; Krech, Till; Krech, Rainer Horst; Jacobsen, Frank; Burandt, Eike.
in: MOL CLIN ONCOL, Jahrgang 15, Nr. 4, 203, 10.2021.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - High mitochondrial content is associated with breast cancer aggressiveness
AU - Lebok, Patrick
AU - Schütt, Katharina
AU - Kluth, Martina
AU - Witzel, Isabell
AU - Wölber, Linn
AU - Paluchowski, Peter
AU - Terracciano, Luigi
AU - Wilke, Christian
AU - Heilenkötter, Uwe
AU - Müller, Volkmar
AU - Schmalfeldt, Barbara
AU - Simon, Ronald
AU - Sauter, Guido
AU - Von Leffern, Ingo
AU - Krech, Till
AU - Krech, Rainer Horst
AU - Jacobsen, Frank
AU - Burandt, Eike
N1 - Copyright: © Lebok et al.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
U2 - 10.3892/mco.2021.2365
DO - 10.3892/mco.2021.2365
M3 - SCORING: Journal article
C2 - 34462659
VL - 15
JO - MOL CLIN ONCOL
JF - MOL CLIN ONCOL
SN - 2049-9450
IS - 4
M1 - 203
ER -
