Elevated Expression of Inhibin α in Prostate Cancer

Abstract

Less than 50% of men who undergo radical prostatectomy for prostate cancer are cured of disease. We evaluate tumor expression of inhibin alpha, a putative tumor suppressor, and the related protein, follistatin, to determine whether expression correlated with failure to be cured by surgery. Tissues were selected from an archival collection of 379 prostatectomy specimens from men with followup of at least 5 years after surgery. Since previous studies showed that such men with only Gleason grade 3 cancer had a greater than 95% chance of no biochemical recurrence (increase in serum prostate specific antigen), our investigation was confined to 174 men with 2% or greater grade 4/5 cancer. These men had an intermediate rate of failure, providing an opportunity to analyze the potential contribution of inhibin alpha or follistatin to progression. Intensity of immunohistochemical labeling for inhibin alpha and follistatin in each cancer was compared with that in normal glands within the same tissue section. The majority of cases showed more intense expression of inhibin alpha in cancer than in normal glands. Those individuals whose cancers had the most elevated expression of inhibin alpha had a higher risk of recurrence, although this association was not statistically significant. Follistatin was expressed equivalently in normal and cancer cells in the majority of cases and did not correlate with recurrence. Our finding that inhibin alpha is frequently overexpressed in high grade prostate cancer suggests that the role of inhibin alpha as a tumor suppressor needs to be reevaluated. Furthermore, assessment of inhibin alpha as a serum marker of prostate cancer, as used to diagnose ovarian cancer, may be warranted.