One of the greatest problems in prostate cancer management today is accurate identification of patients who require treatment for aggressive disease versus those with indolent disease who are suitable for observational strategies. Histological appearance of the tumor, called Gleason score in the prostate cancer field, is the most predictive measure currently used. However, recent studies in multiple tumor types have shown that histological appearance does not always reflect the underlying molecular phenotype of the lesion. Therefore, in prostate cancer specifically, assessment of a molecular marker of androgen receptor driven epithelial differentiation may have clinical predicative capabilities. SAM pointed domain-containing Ets transcription factor (SPDEF) is a potential AR target gene that has shown to be necessary and sufficient for epithelial cell differentiation in many tissues. Although generally associated with good prognosis, SPDEF's role in cancer in unclear. This study demonstrates, through retrospective immunohistochemical analysis, the utility of SPDEF as a predictive biomarker for patients that have an extended benefit from androgen deprivation therapy (ADT). Furthermore, dual roles of SPDEF to inhibit the initiation and supporting the progression of castrate recurrent disease through novel androgen receptor expression regulation in castrate conditions are shown. In ADT naïve patients, SPDEF did not associate with metastatic disease or an induction of epithelial to mesenchymal transition. However, aggressive tumors tended to be larger, have greater SPDEF variability, and lack vimentin expression; a phenotype that could be explained by a partial EMT. In conclusion, SPDEF may be clinically useful to assess the epithelial phenotype of tumors, and could have utility identifying patients that will respond well to androgen deprivation therapy.
|Commitee:||Bakin, Andrei, Campbell, Moray, Foster, Barbara|
|School:||State University of New York at Buffalo|
|Department:||Roswell Park . Pharmacology|
|School Location:||United States -- New York|
|Source:||DAI-B 74/10(E), Dissertation Abstracts International|
|Subjects:||Molecular biology, Cellular biology, Oncology|
|Keywords:||Androgen deprivation therapy, Castration recurrent disease, E26 transcription, Metastasis, Prognosis, Prostate, Prostate cancer, Spdef|
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