Serum S100β

A noninvasive marker of blood-brain barrier function and brain lesions

Authors

  • Andrew A. Kanner M.D.,

    1. Brain Tumor Institute, The Cleveland Clinic, Cleveland, Ohio
    2. Department of Neurosurgery, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    3. Cerebrovascular Research Center, The Cleveland Clinic, Cleveland, Ohio
    Search for more papers by this author
  • Nicola Marchi Ph.D.,

    1. Cerebrovascular Research Center, The Cleveland Clinic, Cleveland, Ohio
    Search for more papers by this author
  • Vincent Fazio M.S.,

    1. Cerebrovascular Research Center, The Cleveland Clinic, Cleveland, Ohio
    Search for more papers by this author
  • Marc R. Mayberg M.D.,

    1. Brain Tumor Institute, The Cleveland Clinic, Cleveland, Ohio
    2. Department of Neurosurgery, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    3. Cerebrovascular Research Center, The Cleveland Clinic, Cleveland, Ohio
    Search for more papers by this author
  • Michael T. Koltz M.S.,

    1. Cerebrovascular Research Center, The Cleveland Clinic, Cleveland, Ohio
    Search for more papers by this author
  • Vitaly Siomin M.D.,

    1. Brain Tumor Institute, The Cleveland Clinic, Cleveland, Ohio
    Search for more papers by this author
  • Glen H. J. Stevens D.O., Ph.D.,

    1. Brain Tumor Institute, The Cleveland Clinic, Cleveland, Ohio
    Search for more papers by this author
  • Thomas Masaryk M.D.,

    1. Cerebrovascular Research Center, The Cleveland Clinic, Cleveland, Ohio
    2. Department of Neurological Surgery, The Cleveland Clinic, Cleveland, Ohio
    Search for more papers by this author
  • Barbara Ayumar B.S.,

    1. Brain Tumor Institute, The Cleveland Clinic, Cleveland, Ohio
    Search for more papers by this author
  • Michael A. Vogelbaum M.D., Ph.D.,

    1. Brain Tumor Institute, The Cleveland Clinic, Cleveland, Ohio
    Search for more papers by this author
  • Gene H. Barnett M.D.,

    1. Brain Tumor Institute, The Cleveland Clinic, Cleveland, Ohio
    Search for more papers by this author
  • Damir Janigro Ph.D.

    Corresponding author
    1. Brain Tumor Institute, The Cleveland Clinic, Cleveland, Ohio
    2. Cerebrovascular Research Center, The Cleveland Clinic, Cleveland, Ohio
    3. Department of Neurological Surgery, The Cleveland Clinic, Cleveland, Ohio
    4. Department of Cell Biology, The Cleveland Clinic, Cleveland, Ohio
    • c/o Martha Tobin, Editorial Services Manager, Department of Neurosurgery, S-80, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195
    Search for more papers by this author
    • Fax: (216) 445-1466

    • Dr. Janigro is a consultant to Sangtec Medical Inc.


Abstract

BACKGROUND

S100β protein is expressed constitutively by brain astrocytes. Elevated S100β levels in cerebrospinal fluid and serum reported after head trauma, subarachnoid hemorrhage, and stroke were correlated with the extent of brain damage. Because elevated serum S100β also was shown to indicate blood-brain barrier (BBB) dysfunction in the absence of apparent brain injury, it remains unclear whether elevation of serum levels of S100β reflect BBB dysfunction, parenchymal damage, or both.

METHODS

The authors conducted a prospective study of serum S100β levels in six patients who underwent hyperosmotic BBB disruption (BBBD) with intraarterial chemotherapy for primary central nervous system lymphoma. In addition, 53 serum S100β samples were measured in 51 patients who had a variety of primary or metastatic brain lesions at the time of neuroimaging.

RESULTS

S100β was correlated directly with the degree of clinical and radiologic signs of BBBD in patients who were enrolled in the hyperosmotic study. In patients with neoplastic brain lesions, gadolinium enhancement on a magnetic resonance image was correlated with elevated S100β levels (n = 45 patients; 0.16 ± 0.1 μg/L; mean ± standard error of the mean) versus nonenhancing scans (n = 8 patients; 0.069 ± 0.04 μg/L). Primary brain tumors (n = 8 patients; 0.12 ± 0.08) or central nervous system metastases also presented with elevated serum S100β levels (n = 27 patients; 0.14 ± 0.34). Tumor volume was correlated with serum S100β levels only in patients with vestibular schwannoma (n = 6 patients; 0.13 ± 0.10 μg/L) but not in patients with other brain lesions.

CONCLUSIONS

S100β was correlated directly with the extent and temporal sequence of hyperosmotic BBBD, further suggesting that S100β is a marker of BBB function. Elevated S100β levels may indicate the presence of radiologically detectable BBB leakage. Larger prospective studies may better determine the true specificity of S100β as a marker for BBB function and as an early detection or follow-up marker of brain tumors. Cancer 2003;97:2806–13. © 2003 American Cancer Society.

DOI 10.1002/cncr.11409

Ancillary