Comparison of total and intact aminoterminal propeptide of type I procollagen assays in patients with breast cancer with or without bone metastases.

Abstract

BACKGROUND:

Aminoterminal propeptide of type I procollagen (PINP) reflects bone formation. Two different antigens exist in human serum: intact PINP and a monomeric form. The intact PINP assay measures trimeric form and the total assay measures both forms. The structure and origin of the monomeric form is still unclear.

METHODS:

Automated intact and total PINP assays were compared in breast cancer patients with (n = 60) or without bone metastases (n = 226). In addition, cross-linked carboxyterminal telopeptide of type I collagen (ICTP) was measured from the same patients and compared with the concentration of PINP monomer (difference between intact and total PINP). Monomeric PINP was purified from human ascitic fluid and characterized by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

RESULTS:

The correlations were good (r > 0.948) between intact PINP and total P1NP in all patient groups. The correlation between the monomeric form and ICTP was lower in patients without bone metastases (r = 0.507) than in patients with bone metastases (r = 0.894). This indicates that the monomeric form reflects the degradation of type I collagen because bone metastases are osteolytic in nature. After several steps in the purification of the monomer form there was a single peak. Only the single band was visible in the SDS-PAGE gel. The alpha1-chain of intact PINP consists of 161 amino acids with a molecular weight of 14224.02. The purified monomer peptide in MALDI-TOF MS was smaller, 10576.41, and most likely cleaved after the arginine residue (amino acid number 120) with a trypsin-like protease.

CONCLUSIONS:

Intact and total PINP assays give similar results in many conditions, but there are differences, for example in breast carcinoma, which should be recognized.

• Authors: Lauri Marin, Marja-Kaisa Koivula, Arja Jukkola-Vuorinen, Aila Leino, Juha Risteli
• Journal: Annals of clinical biochemistry (Ann Clin Biochem) Vol. 48 Issue Pt 5 Pg. 447-51 (Sep 2011) ISSN: 1758-1001 [Electronic] England
• PMID: 21733929 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Peptide Fragments
• Procollagen
• Reagent Kits, Diagnostic
• procollagen Type I N-terminal peptide

Topics

• Ascitic Fluid (chemistry)
• Automation, Laboratory
• Biomarkers, Tumor (blood)
• Bone Neoplasms (secondary)
• Breast Neoplasms (blood, pathology)
• Female
• Humans
• Immunoassay (methods)
• Luminescent Measurements (methods)
• Molecular Weight
• Peptide Fragments (blood, chemistry)
• Procollagen (blood, chemistry)
• Reagent Kits, Diagnostic
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization