High-level expression of protein tyrosine phosphatase non-receptor 12 is a strong and independent predictor of poor prognosis in prostate cancer.

Abstract

BACKGROUND:

Protein tyrosine phosphatase non-receptor 12 (PTPN12) is ubiquitously tyrosine phosphatase with tumor suppressive properties.

METHODS:

PTPN12 expression was analyzed by immunohistochemistry on a tissue microarray with 13,660 clinical prostate cancer specimens.

RESULTS:

PTPN12 staining was typically absent or weak in normal prostatic epithelium but seen in the majority of cancers, where staining was considered weak in 26.5%, moderate in 39.9%, and strong in 4.7%. High PTPN12 staining was associated with high pT category, high classical and quantitative Gleason grade, lymph node metastasis, positive surgical margin, high Ki67 labeling index and early prostate specific antigen recurrence (p < 0.0001 each). PTPN12 staining was seen in 86.4% of TMPRSS2:ERG fusion positive but in only 58.4% of ERG negative cancers. Subset analyses discovered that all associations with unfavorable phenotype and prognosis were markedly stronger in ERG positive than in ERG negative cancers but still retained in the latter group. Multivariate analyses revealed an independent prognostic impact of high PTPN12 expression in all cancers and in the ERG negative subgroup and to a lesser extent also in ERG positive cancers. Comparison with 12 previously analyzed chromosomal deletions revealed that high PTPN12 expression was significantly associated with 10 of 12 deletions in ERG negative and with 7 of 12 deletions in ERG positive cancers (p < 0.05 each) indicating that PTPN12 overexpression parallels increased genomic instability in prostate cancer.

CONCLUSIONS:

These data identify PTPN12 as an independent prognostic marker in prostate cancer. PTPN12 analysis, either alone or in combination with other biomarkers might be of clinical utility in assessing prostate cancer aggressiveness.

• Authors: Sören A Weidemann, Charlotte Sauer, Andreas M Luebke, Christina Möller-Koop, Stefan Steurer, Claudia Hube-Magg, Franziska Büscheck, Doris Höflmayer, Maria Christina Tsourlakis, Till S Clauditz, Ronald Simon, Guido Sauter, Cosima Göbel, Patrick Lebok, David Dum, Christoph Fraune, Simon Kind, Sarah Minner, Jakob Izbicki, Thorsten Schlomm, Hartwig Huland, Hans Heinzer, Eike Burandt, Alexander Haese, Markus Graefen, Asmus Heumann
• Journal: BMC cancer (BMC Cancer) Vol. 19 Issue 1 Pg. 944 (Oct 12 2019) ISSN: 1471-2407 [Electronic] England
• PMID: 31606028 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• ERG protein, human
• Oncogene Proteins, Fusion
• Transcriptional Regulator ERG
• ERBB2 protein, human
• Receptor, ErbB-2
• PTPN12 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 12

Topics

• Aged
• Biomarkers, Tumor (metabolism)
• Cell Proliferation
• Chromosome Deletion
• Follow-Up Studies
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Multivariate Analysis
• Neoplasm Grading
• Oncogene Proteins, Fusion (metabolism)
• PC-3 Cells
• Prognosis
• Prostatectomy
• Prostatic Neoplasms (metabolism, pathology, surgery)
• Protein Tyrosine Phosphatase, Non-Receptor Type 12 (metabolism)
• Receptor, ErbB-2 (metabolism)
• Tissue Array Analysis
• Transcriptional Regulator ERG (metabolism)