Carboxy-terminal telopeptide of type I collagene and tartrate-resistant acid phosphate in patients with colorectal cancer and bone metastases.

Introduction: Despite significant advances in detection and treatment, colorectal cancer (CRC) still remains one of the most prevalent cancers, and one of the leading causes of mortality due to malignancy. In patients with stage I-II CRC surgical resection usually represents the sole treatment, while in those with metastasized tumor (stage IV) any therapy is rarely successful. Unfortunately, up to 60% of patients with CRC undergoing primary surgery with curative intention die from metastatic disease. Thus, occult tumor cells, not detected preoperatively, likely colonize and remain vital in different tissues of these patients, such as lymph nodes, blood, and bone marrow. Usually, CRC metastasizes to the liver and lungs more frequently than to bone. Isolated bone metastasis (BM) is considered truly rare, but it has been observed that the improved survival for patients with metastatic CRC following expanded treatment options is associate with an increased incidence of BMs. Because metastases in uncommon sites often indicates the terminal phase of CRC, clinicians should be more vigilant about possible BMs. For this purpose, several serum biomarkers have been tested for early detection of BMs, such as carboxy-terminal telopeptide of type I collagen (ICTP), a cross-link product of collagen I degradation, and tartrate-resistant acid phosphatase 5b (TRACP), specifically derived from osteoclasts. Recent studies showed that TRACP activity and ICTP were increased in up to 90% of patients with breast cancer and BM. The aim of this study was to evaluate the usefulness of TRACP, ICTP, and bone alkaline phosphatase (BAP) measurements in patients with CRC and BM. Methods: Fourteen patients (9 men, 5 women, mean age 56.1±4.8, range 49-63 years) with CRC and confirmed BMs (cases), and a group of 15 age- and gender matched (10 men, 4 women, age 57.1±4.9 years, p=0.08) patients (controls) without BM (negative F-18 FDG PET/CT) underwent serum TRACP, ICTP, and BAP measurements. Written informed consent was obtained from all the participants. TRACP and BAP were measured by two-site enzyme-linked immunosorbent assay (ELISA), while ICTP was measured by commercially available radioimmunoassay. The sensitivity and specificity of serum TRACP, ICTP, and BAP as a marker for BM were estimated by receiver operator characteristic (ROC) curves. Results: The mean levels of TRACP, ICTP, and BAP (cases vs. controls) were: 5.9 ±1.6 vs. 4.8±1.3 U/L (95% CI 0.11-2.11, p=0.08), 6.9±1.4 vs. 5.9±1.3 U/L (95% CI 0.94-3.04, p=0.0003), and 82.6±18.2 vs. 79.3±16.2 (95% CI 9.81-16.39, p=0.59). ROC analysis established a cutoff value for ICTP of 4.51 U/mL to identify patients with extensive BM with a specificity of 97% and a sensitivity of 92% (area under the curve=0.97; 95% CI=0.95-0.98). A strong relationship was found only between TRACP and ICTP (R=0.95, p<0.0001) serum levels among cases, while there was no correlation between age and biomarkers.