Abstract
Prostate cancer (PC) is a major health problem in the Western world. Current diagnostic tests such as serum prostate specific antigen (PSA), digital rectal examination (DRE) and prostate biopsies each have limitations. PSA may be elevated in non-malignant conditions such as urinary tract infection, prostatitis and benign prostatic hyperplasia. PC screening, risk stratification and monitoring after treatment requires cancer biomarkers with higher sensitivity and specificity for prostate cancer. Cancer biomarkers that could distinguish between clinically significant PC and clinically insignificant disease would help clinicians and patients to avoid over-treatment and under-treatment of localised PC. Engrailed-2 (EN2) is a promising novel biomarker for PC. The EN2 gene is a member of the HOX gene family, which are expressed in the embryonic human brain during development. Several human malignancies, including PC, have demonstrated re-expression of HOX gene products. Human EN2 is protein that is secreted into the urine and may be conveniently assayed using ELISA. Urinary EN2 remains stable at room temperature for up to four days, and there is no requirement for prior DRE. Prostate Histoscanning™ (PHS) is a novel trans-rectal ultrasound-based imaging technique. The manufacturers claim that it has the ability to detect and localise PC. The aim of the studies described in this thesis was to evaluate the roles of EN2 and PHS in the diagnosis of PC, risk stratification of patients diagnosed with localised PC, and the follow up of patients after radical PC treatment. Urinary EN2 was assayed in healthy volunteers and various groups of PC patients. An assay of seminal EN2 was developed, and applied to specimens from healthy volunteers and PC patients. PHS was performed in patients immediately prior to undergoing radical prostatectomy. Urinary EN2 levels were significantly lower among healthy volunteers compared to patients with localised PC (either on active surveillance or before undergoing radical prostatectomy). There was no significant difference between urinary EN2 levels among healthy volunteers and patients who were disease-free five years after radical treatment for PC. There was a strong correlation between urinary EN2 levels and prostate tumour volume among patients undergoing radical prostatectomy. There was no significant difference between urinary EN2 levels before and after neoadjuvant hormone therapy, or before and after prostate brachytherapy. Urinary EN2 levels in the PC relapse group following radical prostatectomy and prostate brachytherapy were significantly higher than among the cured group. Among PC patients, seminal EN2 levels were significantly higher than urinary EN2 levels. We found no correlation between tumour volume and pathological stage measured by PHS versus whole mount RP histology. PHS failed to detect and localise PC in routine clinical practice. However, urinary and seminal EN2 show promise as a PC biomarker.