Insulin-like growth factor-binding protein-2 in patients with prostate carcinoma and benign prostatic hyperplasia

OBJECTIVE Insulin-like growth factor-binding protein (IGFBP)-2 is a major prostatic IGFBP and may be involved in regulating prostate growth. Patients with prostate carcinoma (PC) have elevated serum IGFBP-2 levels which correlate with the specific PC marker, prostate-specific antigen (PSA). The aims of this study were to investigate whether elevated serum IGFBP-2 is unique to PC or also occurs in benign prostatic hyperplasia (BPH), to examine the relations among age, PSA and IGFBP-2 levels, and to examine longitudinal changes in serum IGFBP-2 with PSA in prostate carcinoma. DESIGN AND PATIENTS Sixteen patients (61–83 years) with inoperable PC attending the oncology unit at a tertiary referral hospital were studied. Some serum samples were obtained retrospectively while the majority were collected prospectively over 13 months of treatment. The patients with PC were compared to 8 patients (66–73 years) with histologically proven BPH and 7 male control subjects (61–82 years) with no known prostate abnormality. MEASUREMENTS A new IGFBP-2 RIA was developed. Serum PSA (by EIA), and IGFBP-2, IGFBP-3, IGF-I and IGF-II (by RIA) were measured in all subjects, and serially in patients with PC. RESULTS Serum IGFBP-2 was significantly higher in PC with high PSA (560 ± 66 μg/l, n = 12) than PC with normal PSA (292 ± 65 μg/l, n = 4, P = 0.02), BPH (364 ± 61 μg/l, P = 0.03) and controls (367 ± 44 μg/l, P = 0.04). Mean IGFBP-2 in BPH was not different from controls. IGFBP-2 and PSA were signi- ficantly correlated with age (r = 0.543 and r = 0.433 respectively) and with each other even when the age effect was removed. Serum IGFBP-2 and PSA levels changed concordantly in all 7 PC patients who had serial sampling. Serum IGF-II but not IGF-I or IGFBP-3 was higher in PC and BPH than in controls (PC 332 ± 23 μg/l), BPH 359 ± 26μg/l vs controls 241 ± 37 μg/l; P = 0.03 and 0.02 respectively). CONCLUSIONS Serum IGFBP-2 levels are uniquely elevated in active prostate carcinoma but not in benign prostatic hypertrophy. In PC, serum IGFBP-2 levels closely parallel those of PSA and probably reflect tumour burden. The relation between PSA and IGFBP-2 is partially independent of their individual relations with age. Although serum IGFBP-2 is less sensitive than PSA in PC, it may have adjunctive value in the management of prostate carcinoma.