[Proc Amer Assoc Cancer Res, Volume 45, 2004]
Cellular, Molecular, and Tumor Biology 62: Biomarkers for Metastasis
Bone turnover parameters ICTP and PINP new markers for bone metastases in prostate cancer?
Aristotelis G. Anastasiadis,
Markus Kuczyk and
Eberhard-Karls-University of Tuebingen, Tuebingen, Germany
Skeletal morbidity has a major clinical and socioeconomic significance in prostate cancer (PCa) patients. Unfortunately, imaging studies lack specificity regarding detection of bone metastases and evaluation of therapeutic response. New laboratory parameters that reflect bone metabolism and may discriminate metastasized from non-metastasized patients are therefore urgently needed. Aim of this pilot study was to evaluate the new serum markers carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and the aminoterminal propeptide of type I procollagen (PINP). Serum samples from 44 patients with histologically proven PCa, 23 of those with bone metastases, and from 27 controls with benign prostatic hyperplasia (BPH) were examined. Mean patient age for the PCa and the BPH group was 65 and 69 years, respectively. ICTP (reference values 1.4 - 5.2 ng/ml) and PINP (reference values 21 - 78 ng/ml) were analyzed using specific radioimmunoassays (Orion Diagnostica, Espoo, Finland). Prostate specific antigen (PSA) was measured with the Immulite system (DPC, Los Angeles, CA). Mean serum levels (± SEM) in the control group for PSA (ng/ml), ICTP (ng/ml), and PINP (ng/ml) were 3.22 ± 0.53, 4.36 ± 0.57, and 48.63 ± 9.02, respectively. In PCa patients without and with metastases the values for PSA were 70.74 ± 34.62 and 1,244.26 ± 524.91 (p < 0.05, t-test), for ICTP 5.62 ± 0.63 and 12.35 ± 2.61 (p < 0.05), and for PINP 52.14 ± 8.01 and 232.58 ± 62.47 (p < 0.01), respectively. The area under the receiver operating characteristic (ROC) curve for PSA, ICTP, and PINP was 0.714, 0.658, and 0.654, respectively. Comparisons between the areas were not significantly different. With a specificity of 95.2% for both PSA and ICTP, and of 90.5% for PINP, PSA > 143.0 ng/ml, ICTP > 12.04 ng/ml, and PINP > 109.86 ng/ml was predictive for bone metastases in 47.8%, 34.8%, and in 52.2%, respectively. The bone turnover markers of type I collagen degradation (ICTP) and of type I procollagen synthesis (PINP) might help to better identify PCa patients at high risk for the development of bone metastases. Serial measurements are currently performed on a larger scale to evaluate the role of ICTP and PINP in early detection of progression in patients with PSA failure. In addition, ICTP and PINP may be useful in monitoring therapeutic response to bone metastases after radiation or bisphosphonate therapy.
Copyright © 2004 by the American Association for Cancer Research.