Anti-colony-stimulating Factor-1 Antibody Staining in Primary Breast Adenocarcinomas Correlates with Marked Inflammatory Cell Infiltrates and Prognosis

Background: Clinical studies have shown that a marked lymphoplasmocytic reaction in breast tumors is associated with poor prognosis. Such findings raise the possibility that an inflammatory cell reaction might be a tumor-induced response that tends to promote tumor growth.

Purpose: We assessed the expression of colony-stimulating factor-1 (CSF-1) as well as the prevalence of specific tumor-infiltrating lymphocytes and monocytes in breast tumors.

Methods: Tissue sections were obtained from archival paraffin blocks from 196 breast cancer patients. Seventy-eight percent of the women had been treated by mastectomy and 22% by lumpectomy. Median age of the patients was 54 years, and median follow-up was 7.3 years. Immunohistochemical and in situ hybridization techniques were used to characterize the specimens.

Results: Markedly high numbers of CD45RO-positive T- and L26-positive B-cell infiltrates were found in 13% and 17% of the tissue specimens, respectively. CSF-1 receptor-positive monocytes were detected in 48% and CD68-positive monocytes in 90% of the tumors. In turn, tumors with large fractions of CD68-positive monocytes also showed CSF-1 receptor-positive monocytes (P < .0001). CSF-1 was expressed significantly in 74% of the tumors and the CSF-1 receptor in more than 50% of the tumors. Tumors with high percentages of CSF-1 expressing cells also had marked monocyte infiltrates (P = .035). The presence of marked CD45RO-positive T-cell infiltrates and apparent nuclear staining of CSF-1 in tumor cells were associated with the more frequent occurrence of metastases (P = .02 and P = .04, respectively) and with poor survival (P = .02 and P = .03, respectively).

Conclusions: Large numbers of CD45RO-positive (activated memory but noncytotoxic) T cells as well as a predominant nuclear staining pattern for CSF-1 are associated with a poor outcome in breast cancer patients.

Implications: Nuclear retention of CSF-1 could reflect CSF-1 turnover and function in tumor cells, but new approaches are needed to establish the significance of these observations. Secreted CSF-1 appears to cause monocyte recruitment and activation, thereby modulating immune functions and potentially the expression of the CD45RO phenotype in T cells.