Expression of insulin-like growth factor binding protein-3 before and after neoadjuvant hormonal therapy in human prostate cancer tissues: correlation with histopathologic effects and biochemical recurrence.
OBJECTIVE
To determine the effects of neoadjuvant hormonal therapy (NHT) on insulin-like growth factor binding protein (IGFBP)-3 expression and whether IGFBP-3 expression influences the pathologic effect of NHT and biochemical recurrence after radical prostatectomy in patients with prostate cancer. IGFBP-3 has pro-apoptotic activity, and its expression correlates negatively with prostate cancer cell growth. Castration induces IGFBP-3 expression and apoptosis in the rat prostate.


METHODS
We used tissue specimens from 42 patients who underwent NHT and radical prostatectomy. The pre-NHT and post-NHT specimens were examined for expression of IGFBP-3 using an immunohistochemical technique and for apoptosis using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method. The histopathologic effect was evaluated by the standardized rules for estimating the response of prostate cancer to NHT, determined by the percentage of remaining viable cancer cells, as advocated by the General Rule for Clinical and Pathological Study on Prostate Cancer published by the Japanese Urological Association.


RESULTS
NHT resulted in a statistically significant increase in IGFBP-3 expression compared with baseline (P = 0.01). Such an increase in expression correlated significantly with the induction of apoptotic cells (r = 0.40 and P = 0.01). The post-NHT/pre-NHT IGFBP-3 ratio was significantly greater in the NHT-effective group than in the NHT-noneffective group (P = 0.02). Patients with high IGFBP-3 expression in the post-NHT specimens had a good prognosis (P = 0.03, log-rank test).


CONCLUSIONS
Induction of IGFBP-3 by NHT was associated with apoptosis and a histopathologic effect. IGFBP-3 expression in post-NHT specimens is a potentially useful predictor of biochemical recurrence in patients with prostate cancer.
Miyata
Yasuyoshi
Y
Department of Urology, Nagasaki University Graduate School of Medicine, Nagasaki, Japan.
Sakai
Hideki
H
Kanda
Shigeru
S
Igawa
Tsukasa
T
Hayashi
Tomayoshi
T
Kanetake
Hiroshi
H
D000368:Aged; D000726:Androgen Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D003593:Cytoplasm / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors*; D006801:Humans; D007150:Immunohistochemistry; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
D000726:Androgen Antagonists; D014408:Biomarkers, Tumor; D018972:Insulin-Like Growth Factor Binding Protein 3; D007987:Gonadotropin-Releasing Hormone