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.


OBJECTIVE
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.


CONCLUSIONS
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.
Scholl
S M
SM
Département de Médecine Oncologique, Institut Curie, Paris, France.
Pallud
C
C
Beuvon
F
F
Hacene
K
K
Stanley
E R
ER
Rohrschneider
L
L
Tang
R
R
Pouillart
P
P
Lidereau
R
R
D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D002467:Cell Nucleus / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000502:physiology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis
D016173:Macrophage Colony-Stimulating Factor