Relationship between changes in prostate cancer cell proliferation, apoptotic index, and expression of apoptosis-related proteins by neoadjuvant hormonal therapy and duration of such treatment.
OBJECTIVE
To investigate the relationships between changes in the carcinoma cell proliferation index, apoptotic index (AI), and apoptosis-related factors, including bcl-2 and bax, after different durations of neoadjuvant hormonal therapy (NHT) in prostate cancer tissue.


METHODS
Pre- and post-NHT specimens were obtained from 42 patients who had undergone NHT and radical prostatectomy. The patients were divided into two groups according to the duration of NHT: group 1 (3 to 7 months, n = 21) and group 2 (8 to 12 months, n = 21; no randomization). Immunohistochemistry was used to determine the expression of bcl-2 and bax and to determine the proliferation index, and the terminal deoxynucleotidyl transferase-mediated nick end-labeling method was used to assess apoptosis and determine the AI.


RESULTS
The median proliferation indexes of groups 1 (1.8%) and 2 (1.6%) were significantly lower than the respective values in the pre-NHT specimens (4.9%, P < 0.01). The median AI of group 1 (2.5%) was greater than in the pre-NHT specimens (1.4%). In addition, the post/pre-NHT AI ratio correlated significantly with the duration of NHT in group 1 (r = 0.58, P < 0.01), but not in group 2. Bax expression increased in a manner parallel to that of the AI.


CONCLUSIONS
NHT suppresses prostate cancer cell proliferation for 3 to 12 months. Although the AI was increased during 3 to 7 months of NHT, no significant difference was found between the pre-NHT levels and those after 8 to 12 months. Our results support the current belief that the optimal duration of NHT is longer than 3 months.
Miyata
Yasuyoshi
Y
Department of Urology, Nagasaki University School of Medicine, Nagasaki, Japan. int.doc.miya@m3.dion.ne.jp
Kanda
Shigeru
S
Sakai
Hideki
H
Hakariya
Tomoaki
T
Kanetake
Hiroshi
H
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017209:Apoptosis; D049109:Cell Proliferation; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D020360:Neoadjuvant Therapy; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D018931:Antineoplastic Agents, Hormonal; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein