Adjunctive value of cell proliferation but not of apoptosis to interpret pathologic effects on prostatic cancer after neoadjuvant endocrine therapy.
BACKGROUND
The current histological evaluation of the effects of endocrine therapy has difficulty in distinguishing pathologic degeneration caused by androgen ablation from residual poorly differentiated tumor. Therefore, we examined the changes in cell proliferation and apoptosis before and after endocrine therapy and analyzed whether they correlated with pathologic effects and histological differentiation.


METHODS
Between January 1986 and December 1995, 52 patients with clinical stage B2 and C prostate cancer underwent radical prostatectomy after neoadjuvant endocrine therapy (median duration 3.8 months). Proliferative and apoptotic activities of pretreatment biopsy specimens and radical prostatectomy specimens were analyzed with MIB-1 monoclonal antibody and in situ end-labeling of fragmented DNA.


RESULTS
The mean proliferative index (PI) of radical prostatectomy specimens was significantly lower than that of biopsy specimens (P = 0.000003) and the decrease in PI after endocrine therapy was significantly related to histological differentiation (P = 0.014). There was a weak relationship between the decrease in PI after endocrine therapy and pathologic effects (P = 0.054), while in pathologically effective cases (Grades 2 and 3), three out of 16 (19%) showed a < 50% decrease in PI after endocrine therapy, and may be regarded as having poorly differentiated tumors. The mean apoptotic index (AI) of prostatectomy specimens tended to be higher than that of biopsy specimens (P = 0.054). The increase in AI after endocrine therapy was not related to histological differentiation and pathologic effects.


CONCLUSIONS
Pathologic effects caused by endocrine therapy may be in part misled by routine histopathologic staining and the change in PI may help in recognizing the pathologic effects of endocrine therapy and have adjunctive value for the interpretation of the effects of endocrine therapy.
Maeda
O
O
Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
Kinouchi
T
T
Meguro
N
N
Saiki
S
S
Kuroda
M
M
Usami
M
M
Wada
A
A
Kotake
T
T
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017209:Apoptosis; D002455:Cell Division; D017024:Chemotherapy, Adjuvant; D004054:Diethylstilbestrol / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery
D018931:Antineoplastic Agents, Hormonal; D007987:Gonadotropin-Releasing Hormone; D004054:Diethylstilbestrol