Up-regulation of neuroendocrine differentiation in prostate cancer after androgen deprivation therapy, degree and androgen independence

The up-regulation of neuroendocrine (NE) differentiation after hormonal therapy, as well as the relationship between the degree of NE differentiation and androgen independence was investigated. One hundred and thirty-seven whole prostate specimens that were derived from surgery and autopsy (group A: no hormonal therapy, 44 patients; group B: with hormonal therapy less than 12 months, 25 patients; group C: with hormonal therapy more than 13 months, 68 patients) were studied. Neuroendocrine differentiation was evaluated by immunostaining with chromogranin A. The degree of NE differentiation was evaluated by the percentage area of positive NE cell expression (grade 0, negative; grade 1, 1-33%; grade 2, 34-66%; grade 3, 67-100%). The degree of NE differentiation was compared in androgen-independent and -dependent tumors in group C. Neuroendocrine differentiation was expressed as 31.8% in group A, 44% in group B and 70.5% in group C (p <0.001, Chi-squared test). Group C included 20 androgen-independent cases in which 3 cases were grade 0, 2 were grade 1, 6 were grade 2 and 9 were grade 3. Conversely, for androgen-dependent cases, there were 16, 16, 11 and 5 cases, respectively. Neuroendocrine cells, whether positive or not, alone was not significantly different (p=0.124, Chi-squared test); however, the percentage area of positive NE cell expression was significantly different between the androgen-independent and -dependent tumors (p=0.0044, Chi-squared test). Hormonal therapy may play an important role in the up-regulation of NE differentiation. As well as NE cell expression, whether positive or not, the degree of expression should also be observed to evaluate a poor prognosis, tumor progression and androgen independence.