Endocrine Abstracts

Background: Prostate cancer is the second leading cause of cancer-related deaths in men worldwide. A marker of poor survival in prostate cancer patients is the loss of the tumor suppressor gene PTEN (phosphoinositide-3-phosphatase). Deletion of PTEN occurs in approximately 40% of prostate cancer patients, and is associated with early biochemical recurrence, metastatic potential, and androgen-independence. Androgen-deprivation-therapy (ADT) remains the principal treatment of prostate cancer, despite the eventual resistance to treatment in most patients. The exact mechanism of such ADT resistance is yet to be confirmed. Thus, our study aimed to determine whether PTEN mutations play a role in ADT resistance in prostate cancer.

Methods: A case–control study was performed. Cases (n=64) were patients with confirmed diagnosis of prostate cancer treated with ADT, while controls (n=58) were subjects with benign prostatic hyperplasia. Prostate specimens were collected by needle core biopsy, or during transurethral resection of the prostate or radical prostatectomy. PTEN expression status was assessed by immunohistochemistry, and scores of 0 (no expression) and 1 (expression) were assigned to prostate tissues.

Results: Loss of PTEN expression (score 0) was 30 times more likely to occur in prostate cancer cases compared to controls. However, the presence of PTEN mutation was not significantly correlated with the pathological Gleason grade of prostate cancer severity. Mean time to ADT resistance in prostate cancer patients was 25.3 months, which was not significantly different between those with PTEN mutation (mean=26.8 months) and those without mutation (mean=23.5 months). However, there was a statistically significant difference in mean time to ADT resistance between those receiving the combined therapy (mean=33.2 months) and those receiving either goserline alone (mean=9 months) or triptoline alone (mean=8.9 months).

Conclusion: Our results indicate that loss of PTEN expression is not sufficient to explain ADT resistance in prostate cancer patients. Combined hormonal therapy might be a promising strategy to slow the process of ADT resistance in these patients. However, further studies in larger prospective cohorts are warranted.