Abstract
BackgroundProtein tyrosine phosphatase non-receptor 12 (PTPN12) is ubiquitously tyrosine phosphatase with tumor suppressive properties.MethodsPTPN12 expression was analyzed by immunohistochemistry on a tissue microarray with 13,660 clinical prostate cancer specimens.ResultsPTPN12 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.ConclusionsThese 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.
Highlights
Protein tyrosine phosphatase non-receptor 12 (PTPN12) is ubiquitously tyrosine phosphatase with tumor suppressive properties
A number of studies have reported that decreased expression of PTPN12 as determined by immunohistochemistry was found to be significantly associated with advanced tumor stage in hepatocellular [10, 11], renal cell [12], and urinary bladder [13] as well as in squamous cell carcinoma of the oral cavity, esophagus and nasopharynx [14,15,16,17]
High level PTPN12 staining was associated with advanced pT category, high conventional and quantitative Gleason grade, and positive surgical margin status and to a higher likelihood for prostate specific antigen (PSA) recurrence (p < 0.0001 each)
Summary
Protein tyrosine phosphatase non-receptor 12 (PTPN12) is ubiquitously tyrosine phosphatase with tumor suppressive properties. The currently available criteria used for the distinction between high risk and low risk patients, such as Gleason grade, clinical stage and prostate specific antigen (PSA) level, are statistically powerful but not sufficient to enable optimal treatment decisions for every patient. Protein tyrosine phosphatase non-receptor 12 (PTPN12) is a member of the protein tyrosine phosphatases family, which is ubiquitously expressed [3, 4]. It dephosphorylates cellular tyrosine kinases, such as HER2 [5] and functions as a tumor suppressive key regulator of signaling pathways involved in cell-extracellular matrix crosstalk, cellular responses to mechanical stress and cell adhesion [6, 7]. High PTPN12 expression was described to be linked with favorable survival duration in non-small cell lung carcinoma patients [18] and with response to neoadjuvant chemotherapy in triple negative breast cancer [19]
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