Central nervous system (CNS) diagnostics is a promising tool for detection of neurological disorders, including brain metastases. One of the earliest applications of CNS diagnostics was based on serum markers of blood‐brain barrier (BBB) dysfunction, which often correlates with acute, chronic, or incipient brain disease. In the case of brain metastases, serum levels of S100β demonstrated a good negative predictive value comparable to radiologic investigations. However, a confounding factor was the presence of BBB changes due to cerebrovascular disease.

Of 103 patients enrolled in a lung cancer study, greater than 50% presented with magnetic resonance imaging (MRI) changes consistent with chronic cerebrovascular disease and reflected by elevated serum S100β. To unveil serum protein, the authors used proteomic techniques that allow discrimination between patients with brain metastases and lung cancer patients affected by cerebrovascular ischemic changes without infiltrating tumor.

ProApolipoprotein A1, transferrin, haptoglobin, and transthyretin were upregulated in patients affected by chronic cerebrovascular disease and brain metastases compared with those affected only by vascular diseases. ProApolipoprotein A1 was significantly increased (p < .05) in patients with CNS disease.

In conclusion, these data support the use of serum markers for the early detection of brain metastases. ProApolipoprotein A1 may be used in conjunction with S100β for serum‐based, MRI‐independent diagnosis of metastatic brain tumors. Cancer 2008. ©2008 American Cancer Society.