Aberrant expression of the microtubule-associated protein tau is an independent prognostic feature in prostate cancer.

Abstract

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.

• Authors: Cornelia Schroeder, Jan Grell, Claudia Hube-Magg, Martina Kluth, Dagmar Lang, Ronald Simon, Doris Höflmayer, Sarah Minner, Eike Burandt, Till S Clauditz, Franziska Büscheck, Frank Jacobsen, Hartwig Huland, Markus Graefen, Thorsten Schlomm, Guido Sauter, Stefan Steurer
• Journal: BMC cancer (BMC Cancer) Vol. 19 Issue 1 Pg. 193 (Mar 01 2019) ISSN: 1471-2407 [Electronic] England
• PMID: 30823906 (Publication Type: Journal Article)

Chemical References

• MAPT protein, human
• Oncogene Proteins, Fusion
• TMPRSS2-ERG fusion protein, human
• tau Proteins
• PTEN Phosphohydrolase
• PTEN protein, human
• KLK3 protein, human
• Kallikreins
• Prostate-Specific Antigen

Topics

• Humans
• Immunohistochemistry
• Kallikreins (blood)
• Lymph Nodes (pathology)
• Male
• Multivariate Analysis
• Neoplasm Grading
• Neoplasm Recurrence, Local (blood, epidemiology)
• Neoplasm Staging
• Oncogene Proteins, Fusion (genetics)
• PTEN Phosphohydrolase (genetics)
• Prognosis
• Proportional Hazards Models
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms (genetics, metabolism, pathology)
• tau Proteins (metabolism)