Insulin-like growth factor binding protein 2: an androgen-dependent predictor of prostate cancer survival.
BACKGROUND
Evidence suggests that the insulin-like growth factor (IGF) family is important in prostate cancer. We evaluate the ability of IGF markers to predict biochemical recurrence-free survival (bRFS) following radical prostatectomy (RRP).


METHODS
Preoperative sera from 141 patients undergoing RRP were analyzed for IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3. A multivariate Cox model was created to assess the ability of these markers to predict bRFS. Preoperative covariables included: biopsy Gleason score, clinical TNM stage, serum PSA and neoadjuvant hormonotherapy. Kaplan-Meier curves were stratifying by IGF cutpoints (determined by ROC analysis) and hormonotherapy status.


RESULTS
Average follow-up was 6.92 years, median PSA was 6.9 ng/ml and 85.1% of patients had cT2NxM0 disease. 49 patients experienced a PSA failure. Average levels of IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3 were 156.5 ng/ml, 48.1 ng/ml, 396.8 ng/ml and 3303.7 ng/ml, respectively. IGFBP-2 was an independent predictor of PSA failure. Patients treated with neoadjuvant ADT (n=71) and whom had high IGFBP-2 levels experienced a 5-year bRFS that was better than those with low IGFBP-2 levels (77.7% vs. 53.3%). Patients without neoadjuvant ADT whom had high IGFBP-2 levels had a 5-year bRFS that was worse than those with low IGFBP-2 levels (64.5% vs. 82.7%).


CONCLUSIONS
Preoperative IGFBP-2 predicts post-radical prostatectomy bRFS and is independent of stage, Gleason score and PSA. Increased IGFBP-2 is associated with better survival in patients with neoadjuvant hormonotherapy but worse survival in those without, suggesting a dramatic switch in function of this protein dependent on the presence or absence of androgens.
Inman
Brant A
BA
Division of Urology, Laval University, CRHDQ, 11 côte du Palais, Québec, QC, Canada G1R 2J6. brantinman@videotron.ca
Harel
François
F
Audet
Jean-François
JF
Meyer
François
F
Douville
Pierre
P
Fradet
Yves
Y
Lacombe
Louis
L
D000230:Adenocarcinoma / Q000097:blood* / Q000473:pathology / Q000628:therapy; D000368:Aged; D000728:Androgens / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D001706:Biopsy; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000628:therapy; D011792:Quebec / Q000453:epidemiology; D012372:ROC Curve; D012189:Retrospective Studies
D000728:Androgens; D014408:Biomarkers, Tumor; D018971:Insulin-Like Growth Factor Binding Protein 2; D017430:Prostate-Specific Antigen