Evaluation of an Epithelial Plasticity (EP) Biomarker Panel in Men with Localized Prostate Cancer

BACKGROUND: Given the potential importance of epithelial plasticity (EP) to cancer metastasis, we sought to investigate biomarkers related to EP in men with localized prostate cancer (PC) for the association with time to PSA recurrence and other clinical outcomes after surgery. METHODS: Men with localized PC treated with radical prostatectomy at the Durham VA medical center and whose prostatectomy tissues were included in a tissue microarray (TMA) linked to long-term outcomes. We performed immunohistochemical studies using validated antibodies against E-cadherin and Ki-67 and mesenchymal biomarkers including N-cadherin, vimentin, SNAIL, ZEB1, and TWIST. Association studies were conducted for each biomarker with baseline clinical/pathologic characteristics and risk of PSA recurrence over time. RESULTS: Two hundred and five men contributed TMA tissue and had long-term follow-up (median 11 years). Forty-three percent had PSA recurrence; 3 died of PC. The majority had high E-cadherin expression (86%); 14% had low/absent E-cadherin expression. N-cadherin was rarely expressed (<4%) and we were unable to identify an E-to-N cadherin switch as independently prognostic. No associations with clinical risk group, PSA recurrence, or Gleason sum were noted for SNAIL, ZEB1, vimentin, or TWIST, despite heterogeneous expression between patients. We observed an association of higher Ki-67 expression with Gleason sum (p=0.043), NCCN risk (p=0.013), and PSA recurrence (HR 1.08, p=0.0095). CONCLUSIONS: The expression of EP biomarkers in this cohort of men with a low risk of PC-specific mortality was not associated with aggressive features or PSA relapse after surgery.