The activated macrophage colony-stimulating factor (CSF-1) receptor as a predictor of poor outcome in advanced epithelial ovarian carcinoma

Abstract

Objective: We have previously shown that the macrophage colony-stimulating factor receptor (CSF-1R) and its ligand, CSF-1, together predict poor prognosis in epithelial ovarian carcinoma. The activated or phosphorylated form of CSF-1R (CSF-1Rphos) has been associated with enhanced invasive and metastatic potential. Our goal is to correlate CSF-1Rphos with known prognostic factors and to determine its role in predicting outcome in advanced ovarian cancer.

Methods: One hundred forty-two primary and forty-seven metastatic epithelial ovarian tumors from 98 patients were immunohistochemically stained using antibodies PY809 and PY723 against their respective tyrosine residues associated with local invasiveness and metastasis. chi2 analysis was used to correlate CSF-1Rphos staining and previously studied prognosticators within each group. Kaplan-Meier curves of survival were comparedusing the log-rank test with significance of P < 0.05.

Results: Forty-seven and nine-tenths percent (68/142) of primary tumors and forty-eight and nine-tenths percent (23/47) of metastatic tumors stained positive for PY809 and PY723, respectively. The PY809+ group was strongly associated with CSF-1R (P = 0.015) as was the PY723+ group (P = 0.025) in its respective subset. CSF-1Rphos by itself was not a predictor of survival or disease-free interval (DFI) in either the primary or metastatic group. However, when combined with CSF-1R in the metastatic group, the two together predicted worse survival (P = 0.007) and decreased DFI (P = 0.011).

Conclusions: Phosphorylated tyrosine kinase receptors are detectable in a significant number of ovarian tumors. Staining strongly correlates with CSF-1R. PY723+ metastases coexpressing CSF-1R portend a highly significant decrease in survival and increased risk of recurrence which may serve to identify high-risk ovarian cancer patients.