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Keywords:

  • glioblastoma;
  • astrocytoma;
  • angiogenesis;
  • hepatocyte growth factor;
  • brain tumors;
  • meningioma

Abstract

BACKGROUND

Hepatocyte growth factor (HGF) is a cytokine that participates in multiple cell functions; it promotes proliferation, motility, and morphogenesis of epithelial cells. Some malignant tumors, such as breast carcinoma, bronchogenic carcinoma, and multiple myeloma, overexpress it and its receptor. Hepatocyte growth factor is also present in normal astrocytes; therefore, it is important to investigate whether HGF participates in the pathophysiology of malignant gliomas and other brain tumors. Intratumoral concentration of HGF in human intracranial neoplasms was measured and correlated with prognosis, tumor recurrence, vasogenic edema, cell proliferation index, and vascular density.

METHODS

Hepatocyte growth factor concentration was measured in 62 intracranial tumors, including 16 anaplasic astrocytomas (AA), 16 glioblastoma multiformes (GM), 11 meningiomas, 9 hypophyseal adenomas, 7 oligodendrogliomas, and 3 cordomas, and in 4 samples of nonneoplastic brain tissue. The following parameters were correlated with HGF values: survival and tumor recurrence, cell proliferation index and vascular density as determined by immunohistopathologic analysis, and peritumoral edema as seen by magnetic resonance imaging.

RESULTS

Hepatocyte growth factor concentration (pg/mL) was significantly higher in malignant gliomas (AA and GM) than in adenomas, oligodendrogliomas, and nonneoplastic brain tissue, but it was similar to that of meningiomas. Mean survival of patients with AA was 16.5 ± 3.6 months and for patients with GM 12.3 ± 1.3 months. Hepatocyte growth factor concentration was higher in GM than in AA (15,844 ± 2504 vs. 7499 ± 1703, P = 0.0375) and was correlated with the cell proliferation index and with poor prognosis. Likewise, mean tumoral concentration of HGF was higher in meningiomas that relapsed than in those without recurrence (22,887 ± 6489 vs. 2090 ± 497, P = 0.008).

CONCLUSIONS

Intratumoral concentration of HGF in gliomas is associated with malignancy and poor prognosis. High HGF is also found in meningiomas and is related with long term recurrence. The current findings suggest that the routine measurement of HGF may be used as a predictive factor for planning therapeutic strategies in both malignant gliomas and meningiomas. The potential use of HGF inhibitors or antagonists for therapy of these tumors should be explored. Cancer 2002;94:3210–8. © 2002 American Cancer Society.

DOI 10.1002/cncr.10594