Neuroendocrine differentiation in hormone refractory prostate cancer following androgen deprivation therapy.

Objective: To evaluate the relationship between neuroendocrine differentiation (NED) status and hormone refractory prostate cancer (HRPC) following hormone therapy based on immunohistochemical study.

Methods: Seventy-two prostate cancer specimens obtained at radical prostatectomy and 21 prostate cancer autopsy specimens from patients who died from HRPC after androgen deprivation therapy were examined for NED status using an antibody against chromogranin A. These specimens were classified into 3 arms: 38 radical prostatectomy specimens from patients with no neoadjuvant hormone therapy (Group 1); 34 from patients with neoadjuvant hormone therapy for 3 to 6 months (Group 2); and 21 autopsy specimens from patients with HRPC following androgen deprivation therapy for more than 1 year (Group 3). Staining of prostatic carcinoma was scored as: 0 = no staining; 1 = staining cells <10%; 2 = staining cells 10-20%; and 3 = staining cells >20%. Differences in scores among the groups were compared using the Kruskal-Wallis rank test. Multivariate analysis using a logistic regression model was performed to examine whether NED status was associated with pathological stage (pT), grade and group.

Results: Forty-nine (53%) tumors had CgA stained cells. NED status increased with longer duration of hormone therapy (p<0.0001). The mean staining score (and standard deviation) was 0.4+/-0.7 in Group 1, 0.7+/-0.7 in Group 2, and 1.4+/-1.1 in Group 3, respectively. By multivariate analysis Group 3 had a relative risk of 5.46 (95%CI 1.28-23.29) for NED compared to the other groups. But other variables were not related to NED. HRPC following Long-term hormonal therapy was the only independent predictor of NED.

Conclusions: The results of this study demonstrated that NED status was significantly increased in patients with HRPC following long-term androgen deprivation therapy, but it could not be discriminate whether the increase of NED is attributable to condition of hormone refractoriness or long-term hormonal therapy.