High mitochondria content is associated with prostate cancer disease progression
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High mitochondria content is associated with prostate cancer disease progression. / Grupp, Katharina; Jedrzejewska, Karolina; Tsourlakis, Maria Christina; Koop, Christina; Wilczak, Waldemar; Adam, Meike; Quaas, Alexander; Sauter, Guido; Simon, Ronald; Izbicki, Jakob Robert; Graefen, Markus; Huland, Hartwig; Schlomm, Thorsten; Minner, Sarah; Steurer, Stefan.
in: MOL CANCER, Jahrgang 12, Nr. 1, 01.01.2013, S. 145.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - High mitochondria content is associated with prostate cancer disease progression
AU - Grupp, Katharina
AU - Jedrzejewska, Karolina
AU - Tsourlakis, Maria Christina
AU - Koop, Christina
AU - Wilczak, Waldemar
AU - Adam, Meike
AU - Quaas, Alexander
AU - Sauter, Guido
AU - Simon, Ronald
AU - Izbicki, Jakob Robert
AU - Graefen, Markus
AU - Huland, Hartwig
AU - Schlomm, Thorsten
AU - Minner, Sarah
AU - Steurer, Stefan
PY - 2013/1/1
Y1 - 2013/1/1
N2 - BACKGROUND: Mitochondria are suggested to be important organelles for cancer initiation and promotion. This study was designed to evaluate the prognostic value of MTC02, a marker for mitochondrial content, in prostate cancer.METHODS: Immunohistochemistry of using an antibody against MTC02 was performed on a tissue microarray (TMA) containing 11,152 prostate cancer specimens. Results were compared to histological phenotype, biochemical recurrence, ERG status and other genomic deletions by using our TMA attached molecular information.RESULTS: Tumor cells showed stronger MTC02 expression than normal prostate epithelium. MTC02 immunostaining was found in 96.5% of 8,412 analyzable prostate cancers, including 15.4% tumors with weak, 34.6% with moderate, and 46.5% with strong expression. MTC02 expression was associated with advanced pathological tumor stage, high Gleason score, nodal metastases (p < 0.0001 each), positive surgical margins (p = 0.0005), and early PSA recurrence (p < 0.0001) if all cancers were jointly analyzed. Tumors harboring ERG fusion showed higher expression levels than those without (p < 0.0001). In ERG negative prostate cancers, strong MTC02 immunostaining was linked to deletions of PTEN, 6q15, 5q21, and early biochemical recurrence (p < 0.0001 each). Moreover, multiple scenarios of multivariate analyses suggested an independent association of MTC02 with prognosis in preoperative settings.CONCLUSIONS: Our study demonstrates high-level MTC02 expression in ERG negative prostate cancers harboring deletions of PTEN, 6q15, and 5q21. Additionally, increased MTC02 expression is a strong predictor of poor clinical outcome in ERG negative cancers, highlighting a potentially important role of elevated mitochondrial content for prostate cancer cell biology.
AB - BACKGROUND: Mitochondria are suggested to be important organelles for cancer initiation and promotion. This study was designed to evaluate the prognostic value of MTC02, a marker for mitochondrial content, in prostate cancer.METHODS: Immunohistochemistry of using an antibody against MTC02 was performed on a tissue microarray (TMA) containing 11,152 prostate cancer specimens. Results were compared to histological phenotype, biochemical recurrence, ERG status and other genomic deletions by using our TMA attached molecular information.RESULTS: Tumor cells showed stronger MTC02 expression than normal prostate epithelium. MTC02 immunostaining was found in 96.5% of 8,412 analyzable prostate cancers, including 15.4% tumors with weak, 34.6% with moderate, and 46.5% with strong expression. MTC02 expression was associated with advanced pathological tumor stage, high Gleason score, nodal metastases (p < 0.0001 each), positive surgical margins (p = 0.0005), and early PSA recurrence (p < 0.0001) if all cancers were jointly analyzed. Tumors harboring ERG fusion showed higher expression levels than those without (p < 0.0001). In ERG negative prostate cancers, strong MTC02 immunostaining was linked to deletions of PTEN, 6q15, 5q21, and early biochemical recurrence (p < 0.0001 each). Moreover, multiple scenarios of multivariate analyses suggested an independent association of MTC02 with prognosis in preoperative settings.CONCLUSIONS: Our study demonstrates high-level MTC02 expression in ERG negative prostate cancers harboring deletions of PTEN, 6q15, and 5q21. Additionally, increased MTC02 expression is a strong predictor of poor clinical outcome in ERG negative cancers, highlighting a potentially important role of elevated mitochondrial content for prostate cancer cell biology.
U2 - 10.1186/1476-4598-12-145
DO - 10.1186/1476-4598-12-145
M3 - SCORING: Journal article
C2 - 24261794
VL - 12
SP - 145
JO - MOL CANCER
JF - MOL CANCER
SN - 1476-4598
IS - 1
ER -