Overexpression of epithelial macrophage colony-stimulating factor (CSF-1) and CSF-1 receptor: a poor prognostic factor in epithelial ovarian cancer, contrasted with a protective effect of stromal CSF-1

Markedly elevated levels of macrophage colony-stimulating factor (CSF-1) in the serum and ascites of epithelial ovarian cancer patients have been previously associated with a poor prognosis. However, measurements of circulating CSF-1 cannot separate CSF-1 originating in the cancer cell from that originating in stromal macrophage or fibroblast. To study the prognosis related to expression of CSF-1 and its receptor in primary and metastatic ovarian cancers and to compare the significance of epithelial versus stromal CSF-1 expression, an immunohistochemical study of 130 ovarian carcinomas was performed. Twenty-two stage I and II and 108 stage III and IV primary tumors were studied. Metastatic lesions were also studied in 96 of these 130 cases, 90 of which came from those cases with advanced-stage disease. The intensity and extent of staining for CSF-1 in epithelium and stroma and for epithelial CSF-1 receptor was scored. Kaplan-Meier curves of survival were compared with the log-rank test. The Cox regression model was used for multivariate analysis. In the primary tumors, there was strong expression of CSF-1 receptor in 65%, epithelial CSF-1 in 36%, and stromal CSF-1 in 22%. In the metastases, there was strong staining for CSF-1 receptor in 65%, epithelial CSF-1 in 41%, and stromal CSF-1 in 15%; strong staining for both CSF-1 receptor and epithelial CSF-1 was noted in 26% of the cases. When the metastases expressed both CSF-1 receptor and epithelial CSF-1 strongly, a significant decrease in disease-free survival in stage III invasive ovarian cancers was observe (P = 0.043), which was found to be an independent prognostic factor (P = 0.007), with an increased relative risk of recurrence of 2.3-fold. Although strong staining for stromal CSF-1 in the primary tumor was not found to have prognostic value, for all stages and for the subsets of stages III and IV and for stage III alone, the finding of any degree of stromal CSF-1 expression in the ovary was a favorable prognostic factor for disease-free (P = 0.046) and overall (P = 0.015) survival. This finding was associated with younger patients (P = 0.007) and low-grade tumors (P = 0.033) and was not an independent prognostic factor on multivariate analysis. Among the primary tumors, there was a significant association (P = 0.022) between stromal CSF-1 staining and lack of strong coexpression of CSF-1 receptor and epithelial CSF-1; 67 of 94 cases shared these features in the primary tumors. In the metastases of in