title: Type I collagen biomarkers in the diagnosis of bone metastases in breast cancer, lung cancer, urinary bladder cancer and prostate cancer. Comparison to CEA, CA 15-3, PSA and bone scintigraphy.
abstract: OBJECTIVE
  In this study we evaluated the clinical usefulness of serum pro-I collagen peptide (PICP) and I collagen telopeptide (ICTP) as indicators of early bone metastases in patients with breast (BC), lung (LC), urinary bladder (UBC) and prostate cancer (PC).
  
  
  METHODS
  305 patients were examined. 145 had histologically confirmed BC (92 with bone metastases), 20 UBC (6 with bone metastases), 11 LC (3 with bone metastases) and 129 PC (68 with bone metastases). In BC patients we compared the PICP and ICTP levels with those of CA 15-3, CEA and bone scintigraphy. Patients with LC and UBC had PICP and ICTP measurements, PC patients had serum PICP, prostate specific antigen (PSA) measurements and bone scans. 104 healthy individuals served as controls.
  
  
  RESULTS
  ICTP and CA 15-3 levels were significantly higher in patients with BC and bone metastases in comparison to patients without metastases (p <0.05), while PICP and CEA were only marginally higher. Significant correlation was observed between existence of bone metastases and ICTP levels (p <0.05). The sensitivity of PICP, ICTP, CEA and CA 15-3 was 28.1, 48.6, 42, and 78%, respectively and specificity was 83.9, 94, 65 and 86%, respectively. ICTP and CA 15-3 were the most reliable markers for early diagnosis of bone metastases in BC. PICP alone or with ICTP were not sensitive enough. Only CA 15-3 showed sensitivity 78% and specificity 86%. When combined CA 15-3, ICTP and CEA the sensitivity and specificity increased to 82% and 96%, respectively. Furthermore, PICP and PSA levels were significantly higher in patients with PC and bone metastases in comparison to patients with benign prostate hyperplasia (BPH) (p <0.0001) or in patients with PC without bone metastases (p <0.0005 for PICP and p <0.0001 for PSA). The co-evaluation of PICP and PSA improved the sensitivity (78%), specificity (96%), accuracy (97%) and positive predictive value (97%). In LC patients, ICTP levels differed significantly between patients with and without bone metastases (p=0.025). In UBC patients, PICP levels differed significantly between patients with and without bone metastases (p=0.017).
  
  
  CONCLUSIONS
  ICTP and CA 15-3 are the most reliable markers for early diagnosis of bone metastases in BC patients. PICP could be useful for diagnosing early bone metastases of PC and combined with PSA and bone scan can be an additional tool in the follow-up of PC patients. For LC patients, ICTP showed a significant difference in the discrimination of patients with and without bone metastases. In UBC patients, PICP showed a significant difference in the discrimination of patients with and without bone metastases.
authors.affiliation: Department of Nuclear Medicine, Democritus University of Thrace, Alexandroupolis, Greece. azissim@yahoo.gr
authors.forename: A
authors.initials: A
authors.lastname: Zissimopoulos
authors.forename: K
authors.initials: K
authors.lastname: Stellos
authors.forename: D
authors.initials: D
authors.lastname: Matthaios
authors.forename: G
authors.initials: G
authors.lastname: Petrakis
authors.forename: V
authors.initials: V
authors.lastname: Parmenopoulou
authors.forename: F
authors.initials: F
authors.lastname: Babatsikou
authors.forename: E
authors.initials: E
authors.lastname: Matthaiou
authors.forename: E
authors.initials: E
authors.lastname: Theodosiadou
authors.forename: P
authors.initials: P
authors.lastname: Hountis
authors.forename: C
authors.initials: C
authors.lastname: Koutis
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism*; D005260:Female; D006801:Humans; D015592:Immunoradiometric Assay; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology; D012680:Sensitivity and Specificity; D014055:Tomography, Emission-Computed; D001749:Urinary Bladder Neoplasms / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D024042:Collagen Type I; D018396:Mucin-1; D017430:Prostate-Specific Antigen