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High mitochondria content is associated with prostate cancer disease progression.

Grupp K, Jedrzejewska K, Tsourlakis MC, Koop C, Wilczak W, Adam M, Quaas A, Sauter G, Simon R, Izbicki JR, Graefen M, Huland H, Schlomm T, Minner S, Steurer S - Mol. Cancer (2013)

Bottom Line: Results were compared to histological phenotype, biochemical recurrence, ERG status and other genomic deletions by using our TMA attached molecular information.Tumors harboring ERG fusion showed higher expression levels than those without (p < 0.0001).Moreover, multiple scenarios of multivariate analyses suggested an independent association of MTC02 with prognosis in preoperative settings.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr, 52, 20246 Hamburg, Germany. mtsourlakis@uke.de.

ABSTRACT

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.

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Representative pictures of (A) negative, (B) weak, (C) moderate, and (D) strong MTC02 immunostaining in prostate cancer.
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Figure 1: Representative pictures of (A) negative, (B) weak, (C) moderate, and (D) strong MTC02 immunostaining in prostate cancer.

Mentions: MTC02 immunostaining was located in the cytoplasm of prostate cells. Cancer cells showed higher staining intensities as compared to normal prostate glands. No differences in the staining patter of the different prostate cancer subtypes were observed. In prostate cancer, MTC02 immunostaining was found in 96.5% of the 8,412 analyzable prostate cancers and was considered strong in 46.5%, moderate in 34.6% and weak in 15.4% of tumors. Representative images demonstrating MTC02 expression in prostate cancer tissue are given in Figure 1. Strong MTC02 staining was associated with advanced pathological tumor stage, high Gleason grade, positive nodal involvement (p < 0.0001 each), positive surgical margin (p = 0.0005), and early PSA recurrence if all cancers were jointly analyzed (p < 0.0001).


High mitochondria content is associated with prostate cancer disease progression.

Grupp K, Jedrzejewska K, Tsourlakis MC, Koop C, Wilczak W, Adam M, Quaas A, Sauter G, Simon R, Izbicki JR, Graefen M, Huland H, Schlomm T, Minner S, Steurer S - Mol. Cancer (2013)

Representative pictures of (A) negative, (B) weak, (C) moderate, and (D) strong MTC02 immunostaining in prostate cancer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842770&req=5

Figure 1: Representative pictures of (A) negative, (B) weak, (C) moderate, and (D) strong MTC02 immunostaining in prostate cancer.
Mentions: MTC02 immunostaining was located in the cytoplasm of prostate cells. Cancer cells showed higher staining intensities as compared to normal prostate glands. No differences in the staining patter of the different prostate cancer subtypes were observed. In prostate cancer, MTC02 immunostaining was found in 96.5% of the 8,412 analyzable prostate cancers and was considered strong in 46.5%, moderate in 34.6% and weak in 15.4% of tumors. Representative images demonstrating MTC02 expression in prostate cancer tissue are given in Figure 1. Strong MTC02 staining was associated with advanced pathological tumor stage, high Gleason grade, positive nodal involvement (p < 0.0001 each), positive surgical margin (p = 0.0005), and early PSA recurrence if all cancers were jointly analyzed (p < 0.0001).

Bottom Line: Results were compared to histological phenotype, biochemical recurrence, ERG status and other genomic deletions by using our TMA attached molecular information.Tumors harboring ERG fusion showed higher expression levels than those without (p < 0.0001).Moreover, multiple scenarios of multivariate analyses suggested an independent association of MTC02 with prognosis in preoperative settings.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr, 52, 20246 Hamburg, Germany. mtsourlakis@uke.de.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus