Purpose: Androgen deprivation therapy is the primary treatment for advanced prostate cancer but many patients eventually experience progression to hormone refractory status. Understanding the molecular changes after androgen deprivation therapy would help evaluate the efficacy or failure of second line therapies. Therefore, we analyzed the expression of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN), the human epidermal receptor-2 and neuroendocrine differentiation after bicalutamide monotherapy, which is emerging as an alternative treatment for locally advanced prostate cancer. Materials and Methods: Molecular arrangements were evaluated in 107 radical prostatectomy specimens from patients given 150 mg bicalutamide before surgery. Pathological regressive changes, and the correlation of postoperative biochemical failure with the extent of molecular arrangements and pathological effects were analyzed. Results: Patients with minimal regression effects after bicalutamide therapy had advanced pathological stage disease, and tended to have positive chromogranin A expression and PTEN inactivation. Only 4 (3.7%) prostatectomy specimens showed human epidermal receptor-2 immunostaining. The probability of positive chromogranin A expression in the PTEN inactivation group was 2.5-fold (OR 2.5, 95% CI 1.1-5.6, p = 0.023) higher than in the nonPTEN inactivation group. Cox regression analysis revealed that seminal vesicle invasion, PTEN/chromogranin A expression and lymph node invasion were significant variables for time to biochemical recurrence. Conclusions: PTEN inactivation and neuroendocrine differentiation were related to refractoriness to bicalutamide therapy. These results support the hypothesis that neuroendocrine differentiation is caused by activation of the serine threonine kinase Akt pathway, which results from PTEN inactivation.
Bibliographical noteFunding Information:
Supported by a grant from the Korean Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A084120) and a faculty research grant from Yonsei University College of Medicine for 2008 (6-2008-0137).
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