The utility of tissue transglutaminase as a marker of apoptosis during treatment and progression of prostate cancer

Purpose: to determine the extent of cell proliferation and apoptosis during treatment and progression of prostate cancer and to determine whether stai ning for tissue transglutaminase is a better histological marker than TUNEL for neoadjuvant androgen ablation treatment of localized prostate cancer. Materials and Methods: Immunocytochemistry techniques were used on archival prostate tissue from four groups of men: 14 men with BPH, 18 men with untr eated, localized prostate cancer, 21 men with localized prostate cancer who received neoadjuvant hormone therapy prior to prostatectomy and 18 men wit h metastatic androgen-independent prostate cancer. Cell proliferation was e valuated by staining for the Ki67 nuclear antigen, and apoptosis was evalua ted by staining for DNA fragmentation (TUNEL technique) and tissue transglu taminase (tTG). Image analysis was used to quantitate the results. Results: TUNEL staining increased by 37% in localized prostate cancer compa red with BPH, with a further increase of 43% seen after neoadjuvant therapy , although variation was such that neither was statistically significant. I n androgen-independent cancer, TUNEL staining was decreased compared with n eoadjuvant hormone treated cancer (p =0.02). Staining for tTG was not incre ased in untreated prostate cancer compared with]BPH; however, staining more than doubled after neoadjuvant therapy, compared with untreated prostate c ancer (p =0.04). Staining for tTG was markedly decreased in androgen-indepe ndent cancer (p =0.07 compared with BPH and p =0.0004 compared with neoadju vant hormone treated cancer). Ki67 immunoreactivity did not significantly c hange in localized prostate cancer, either before or after neoadjuvant ther apy, compared with BPH, but it more than doubled in androgen-independent pr ostate cancer (p =0.07 compared with BPH and p =0.05 compared with untreate d prostate cancer). Conclusions: This study shows that cell proliferation increases and apoptos is decreases as prostate cancer progresses to androgen independence, and, t hat of the markers used in this study, tissue transglutaminase most accurat ely reflects the anticipated effect of neoadjuvant hormone therapy on local ized prostate cancer. An assessment of these parameters provides a valuable tool for appraising new prostate cancer therapies.