The neutrophil, not the tumor

Abstract

BACKGROUND: Patients with resected breast carcinoma who received granulocyte-colony-stimulating factor (G-CSF)-supported adjuvant chemotherapy exhibited an increase in their serum CA 15-3 levels. The authors investigated the role of G-CSF-induced neutrophil MUC1 expression in this setting. METHODS: Twenty-two patients with resected early breast carcinoma and 6 patients with high-grade lymphoma received chemotherapy cycles with or without G-CSF support. When given, G-CSF was administered for either 5 or 10 days per cycle. Immunocytochemical staining and flow cytometric analysis of peripheral blood neutrophils and bone marrow myeloid cells for MUC1 epitopes were performed during treatment. RESULTS: At baseline, the median serum CA 15-3 was 16 U/mL, with weak MUC1 expression in peripheral neutrophils (median immunocytochemical score [ICCS] = 40, flow cytometric score [FCS] = 211 antibody molecules per neutrophil). For patients receiving chemotherapy cycles with 5-day G-CSF support, median CA 15-3 levels increased moderately (median = 28 U/mL; P = 0.016) and absolute neutrophil counts (ANC) did not increase, whereas ICC staining showed a moderate increase (median ICCS = 105; P = 0.015). For patients receiving chemotherapy cycles with 10-day G-CSF, serum CA 15-3 levels increased 2-4-fold from baseline levels and reached abnormal levels (median = 47; P < 0.0005) and the ANC increased (median = 21,400/mm(3); P = 0.007), whereas significant induction of MUC1 expression occurred in the cell membrane and mostly in the cytoplasm of neutrophils (median ICCS = 162; P = 0.001). Flow cytometry detected increased cytoplasmic, but not surface, neutrophil MUC1 expression in the 10-day G-CSF group only (baseline median FCS = 3975, 4th cycle median = 6327 molecules per cell; P = 0.028). In the bone marrow, induction of MUC1 expression was observed in the 10-day G-CSF group only in band forms and neutrophils, but not in more immature myeloid cells. Serum CA 15-3 levels and ICC score were found to demonstrate a linear relation. When ICCS and ANC were incorporated in a combined score, its relation with serum CA 15-3 levels demonstrated a parabolic (cubic) pattern. Serum CA 15-3 levels, ANC, and neutrophil MUC1 staining returned to baseline after the completion of therapy. No excess of malignant recurrences were observed. CONCLUSIONS: Women with resected breast carcinoma who received G-CSF-primed chemotherapy showed serum CA 15-3 elevation due to an increase in peripheral blood neutrophil number and induced neutrophil cytoplasmic MUC1 expression, which was caused by G-CSF. Physicians should be aware of this interaction.