Doublecortin expression in prostate adenocarcinoma and neuroendocrine tumors.

INTRODUCTION: Recent work using prostate cancer mouse models implicated doublecortin (DCX)-expressing neural progenitor cells in prostate adenocarcinoma, reporting a strong association between DCX expression and histologic grade and clinical outcome. We sought to evaluate the relationship between DCX expression and these variables in human prostate cancer.

METHODS AND MATERIALS: DCX expression was measured in transcriptome-wide microarray data from 18,501 patients with localized prostate cancer and 290 patients with metastatic castration-resistant prostate cancer (mCRPC), and compared across disease states, histologic grades, and clinical outcomes. Biochemical recurrence-free survival (BRFS), metastasis-free survival (MFS) and overall survival (OS) were analyzed using Cox-proportional hazards.

RESULTS: DCX expression was not significantly different between normal prostate (n=29), primary prostate cancer (n=131), or metastases (n=19), and did not increase with grade group in a large cohort of RP samples (n=17,967). Those with DCX expression above and below the median did not have significant differences in BRFS (HR 1.15 [0.88-1.49], p=0.31), MFS (HR 1.2 [0.84-1.7], p=0.3) or OS (HR 1.15 [0.7-1.84], p =0.56). In a cohort of untreated prostate cancer, DCX expression was higher in neuroendocrine tumors (n=10) compared to grade group 5 prostate adenocarcinoma (n=110) (p=0.007). Similarly, in two cohorts with mCRPC (n=290), DCX expression was higher in lesions with neuroendocrine features than adenocarcinoma (p<0.001).

CONCLUSIONS: Contrary to recent data using mouse models, DCX expression did not differ by disease state or outcome, and did not increase with grade in a large dataset of human patients with prostate adenocarcinoma. However, DCX expression appeared to correlate with neuroendocrine histology, a subgroup that can arise de novo or in the castrate-resistant setting. Further work is needed to define the role of DCX and its clinical significance in prostate cancer.