TWIST1-WDR5- Regulates Chromatin to Facilitate Prostate Cancer Metastasis.

TWIST1 is a transcription factor critical for development that can promote prostate cancer metastasis. During embryonic development, TWIST1 and HOXA9 are coexpressed in mouse prostate and then silenced postnatally. Here we report that TWIST1 and HOXA9 coexpression are reactivated in mouse and human primary prostate tumors and are further enriched in human metastases, correlating with survival.

Mismatch repair enzyme expression in primary and castrate resistant prostate cancer.

Objective: Although the utility of immunohistochemistry (IHC) for assessing mismatch repair (MMR) protein expression has been demonstrated in solid tumors including primary prostate cancer (PCa), its utility has not been assessed in castration-resistant PCa (CRPC).

Methods: Tissue microarrays were constructed from 127 radical prostatectomies and 155 CRPC metastases from 50 patients. MMR (MLH1, MSH2, MSH6, and PMS2) expression was assessed by IHC and gene expression arrays.

Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer.

Background: Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence of germline mutations in DNA-repair genes among men with localized prostate cancer who are unselected for family predisposition is insufficient to warrant routine testing, the frequency of such mutations in patients with metastatic prostate cancer has not been established.

Methods: We recruited 692 men with documented metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis.

Epithelial mesenchymal-like transition occurs in a subset of cells in castration resistant prostate cancer bone metastases.

TGFβ is a known driver of epithelial-mesenchymal transition (EMT) which is associated with tumor aggressiveness and metastasis. However, EMT has not been fully explored in clinical specimens of castration-resistant prostate cancer (CRPC) metastases. To assess EMT in CRPC, gene expression analysis was performed on 149 visceral and bone metastases from 62 CRPC patients and immunohistochemical analysis was performed on 185 CRPC bone and visceral metastases from 42 CRPC patients.