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 findings raise the possibility that an inflammatory cell reaction might be a tumor-induced response that tends to promot tumor growth. Purpose: We assessed the expression of colony-stimulating factor-1 (CSF-) 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 beren treated by mastectomy and 22% by lumpectomy. Median age of the patients was 54 years, and median follow-up was 7.3 years. Immuno-histochemical 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-posittive monocytes were detected in 48% and CD68-poistive 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 infiltrated (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 = .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 pooroutcome 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 activations, thereby modulating immune functions and potentially the expression of the CD45RO phenotype in T cells. [J Natl cancer Inst 86:120-126, 1994]