PINP as serum marker of metastatic spread to the bone in breast cancer patients

Abstract

Background: Early detection before scintigraphic appearance of osseous metastatic spread might improve the outcome of breast cancer patients. The amino-terminal propeptide (PINP) of type I collagen as an indicator of bone formation is a very promising candidate among all markers of bone metabolism. We investigated the utility of total PINP in breast cancer patients at different stages of the disease.

Patients and methods: Precision tests using controls and serum pools were done for total PINP on the Elecsys2010 analyzer (electrochemiluminescence immunoassay - ECLLA). Baseline samples of 51 breast cancer patients with metastatic disease plus 11 patients under neoadjuvant treatment were available. Altogether, 38 patients had been diagnosed with bone metastases while 24 had no evidence of metastatic spread to the bone.

Results: For serial precision (intra assay), we found coefficients of variation between 1.2-2%. Total imprecision according to the NCCLS protocol ranged from 1. 7-5.4% only. Retrieval in ring trials was between 94% and 103%. ROC analysis of osseous versus nonosseous metastatic disease revealed an area under the curve (AUC) of 0.72. The sensitivity for the detection of bone lesions was 50% at the preliminary normal cut-off of 95 ng/mL. The baseline levels of the patients with bone metastases were significantly higher than those of patients with visceral of soft tissue spread only (p<0.001). PINP concentrations correlated with osseous spread in terms of number and size of the bone lesions. Generally, non-osseous metastases did not produce elevated PINP levels in only 2/24 patients without bone metastases showing minimally elevated PINP concentrations (95 and 112 ng/ml).

Conclusion: The Elecsys test for total PINP is highly reproducible. PINP concentrations can discriminate patients with bone metastases from those without osseous spread. The moderate sensitivity for the diagnosis of bone lesions may be biologically related to ineffective bone repair in a certain subset of patients. Further studies must focus on the monitoring of patients with elevated baseline levels and on those patients with low PINP levels in the case of otherwise proven bone metastases.