Aberrant expression of the microtubule-associated protein tau is an independent prognostic feature in prostate cancer
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Aberrant expression of the microtubule-associated protein tau is an independent prognostic feature in prostate cancer. / Schroeder, Cornelia; Grell, Jan; Hube-Magg, Claudia; Kluth, Martina; Lang, Dagmar; Simon, Ronald; Höflmayer, Doris; Minner, Sarah; Burandt, Eike; Clauditz, Till S; Büscheck, Franziska; Jacobsen, Frank; Huland, Hartwig; Graefen, Markus; Schlomm, Thorsten; Sauter, Guido; Steurer, Stefan.
in: BMC CANCER, Jahrgang 19, Nr. 1, 01.03.2019, S. 193.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Aberrant expression of the microtubule-associated protein tau is an independent prognostic feature in prostate cancer
AU - Schroeder, Cornelia
AU - Grell, Jan
AU - Hube-Magg, Claudia
AU - Kluth, Martina
AU - Lang, Dagmar
AU - Simon, Ronald
AU - Höflmayer, Doris
AU - Minner, Sarah
AU - Burandt, Eike
AU - Clauditz, Till S
AU - Büscheck, Franziska
AU - Jacobsen, Frank
AU - Huland, Hartwig
AU - Graefen, Markus
AU - Schlomm, Thorsten
AU - Sauter, Guido
AU - Steurer, Stefan
PY - 2019/3/1
Y1 - 2019/3/1
N2 - BACKGROUND: Microtubule-associated protein Tau (MAPT) overexpression has been linked to poor prognosis and decreased response to taxane-based therapies in several cancer types, but its relevance in prostate cancer is unknown.METHODS: In this study, MAPT expression was analyzed by immunohistochemistry on a tissue microarray containing 17,747 prostate cancers.RESULTS: MAPT was absent in normal prostate epithelial cells but detectable in 1004 (8.2%) of 12,313 interpretable cancers. Its expression was associated with advanced tumor stage, high Gleason grade, positive lymph nodes, and early biochemical recurrence (p < 0.0001 each). For example, MAPT was found in 3.6% of 2072 Gleason ≤3 + 3 cancers but in 14.4% of 704 Gleason ≥4 + 4 cancers. High-level MAPT staining was also linked to TMPRSS2:ERG fusions (p < 0.0001). MAPT staining was seen in 15.2 and 16% of cancers with TMPRSS2:ERG fusion detected by immunohistochemistry and fluorescence in-situ hybridization, but in only 3.5 and 3.9% of cancers without ERG staining or ERG rearrangements. Moreover, an association was found between MAPT expression and PTEN deletions, with 19% MAPT positivity in 948 PTEN deleted cancers but only 7% MAPT positivity in 3895 tumors with normal PTEN copy numbers (p < 0.0001). Multivariate analysis revealed that the prognostic value of MAPT was independent from established parameters. Conventional large section analyses showed intratumoral MAPT heterogeneity in all three analyzed cancers.CONCLUSIONS: The results of our study identify MAPT, as a moderate prognostic marker in prostate cancer, whose clinical impact, however, may be limited due to the rarity and heterogeneity of its expression.
AB - BACKGROUND: Microtubule-associated protein Tau (MAPT) overexpression has been linked to poor prognosis and decreased response to taxane-based therapies in several cancer types, but its relevance in prostate cancer is unknown.METHODS: In this study, MAPT expression was analyzed by immunohistochemistry on a tissue microarray containing 17,747 prostate cancers.RESULTS: MAPT was absent in normal prostate epithelial cells but detectable in 1004 (8.2%) of 12,313 interpretable cancers. Its expression was associated with advanced tumor stage, high Gleason grade, positive lymph nodes, and early biochemical recurrence (p < 0.0001 each). For example, MAPT was found in 3.6% of 2072 Gleason ≤3 + 3 cancers but in 14.4% of 704 Gleason ≥4 + 4 cancers. High-level MAPT staining was also linked to TMPRSS2:ERG fusions (p < 0.0001). MAPT staining was seen in 15.2 and 16% of cancers with TMPRSS2:ERG fusion detected by immunohistochemistry and fluorescence in-situ hybridization, but in only 3.5 and 3.9% of cancers without ERG staining or ERG rearrangements. Moreover, an association was found between MAPT expression and PTEN deletions, with 19% MAPT positivity in 948 PTEN deleted cancers but only 7% MAPT positivity in 3895 tumors with normal PTEN copy numbers (p < 0.0001). Multivariate analysis revealed that the prognostic value of MAPT was independent from established parameters. Conventional large section analyses showed intratumoral MAPT heterogeneity in all three analyzed cancers.CONCLUSIONS: The results of our study identify MAPT, as a moderate prognostic marker in prostate cancer, whose clinical impact, however, may be limited due to the rarity and heterogeneity of its expression.
KW - Humans
KW - Immunohistochemistry
KW - Kallikreins/blood
KW - Lymph Nodes/pathology
KW - Male
KW - Multivariate Analysis
KW - Neoplasm Grading
KW - Neoplasm Recurrence, Local/blood
KW - Neoplasm Staging
KW - Oncogene Proteins, Fusion/genetics
KW - PTEN Phosphohydrolase/genetics
KW - Prognosis
KW - Proportional Hazards Models
KW - Prostate-Specific Antigen/blood
KW - Prostatic Neoplasms/genetics
KW - tau Proteins/metabolism
U2 - 10.1186/s12885-019-5390-1
DO - 10.1186/s12885-019-5390-1
M3 - SCORING: Journal article
C2 - 30823906
VL - 19
SP - 193
JO - BMC CANCER
JF - BMC CANCER
SN - 1471-2407
IS - 1
ER -