Background: The decrease in use of hormone replacement therapy among postmenopausal women has been suggested as an explanation for the decrease in breast cancer (BC) incidence registered in recent years. However, a number of patients with small BC may develop aggressive disease, and thus the traditional histopathological characteristics are unable to correctly evaluate the biological behavior of BC. Each tumor is not an isolated entity, but is associated with several host cells, such as endothelial cells, fibroblasts, and immune cells. Monocyte activation plays a role in immune response against cancer, and contributes to cancer cells aggressiveness. The aim of this study was to assess the role of monocyte activation, showed using three monoclonal antibodies against human CD64 (clones 22 and 32.2) and CD163 (clone Mac2-158), in differentiating patients with localized and metastatic BC. Patients and Methods: Sixteen women (median age 47 years, range 32-76 years) with confirmed invasive ductal carcinoma and positive axillary lymph nodes (pN1) who were not currently receiving chemotherapy (cases), and 18 age- and pT-matched pN0 women (controls) were enrolled in the study. The absolute neutrophil and monocyte count was obtained with routine hematological assay, while polymorphonuclear (PMN) CD64 index, monocyte CD64 index (as direct marker of monocyte activation), and monocyte CD163 index were assayed using a specific commercial kit. Each sample (50 μL) was prepared and analyzed by flow cytometry, according to the manufacturer's guidelines. Results: The absolute neutrophil and monocyte counts did not differ (p=NS) between groups (cases vs. controls), as well as PMC CD64 index (7.5±2.3 vs. 8.5±2.1, p=0.19). The monocyte CD64 index was significantly higher in patients with metastatic BC (10.5±2.1 vs. 8.4±1.9, p=0.004), while monocyte CD163 index was lower (2451±256 vs. 2711±365, p=0.024). Conclusions: Usually, PMN CD64 index increases during infections in response to specific cytokines. An elevated monocyte CD64 index suggests that monocyte vs. neutrophil activation may have a role in mediating the response to the presence of metastases, while a lower monocyte CD163 index suggests a scavenger receptor shedding during monocyte activation. These preliminary data confirm the usefulness of monocyte activation markers measurement in patients with metastatic BC.
Role of monocyte activation markers in patients with localized and metastatic breast cancer: Preliminary results.
LUMACHI, FRANCO;FALLO, FRANCESCO
2012
Abstract
Background: The decrease in use of hormone replacement therapy among postmenopausal women has been suggested as an explanation for the decrease in breast cancer (BC) incidence registered in recent years. However, a number of patients with small BC may develop aggressive disease, and thus the traditional histopathological characteristics are unable to correctly evaluate the biological behavior of BC. Each tumor is not an isolated entity, but is associated with several host cells, such as endothelial cells, fibroblasts, and immune cells. Monocyte activation plays a role in immune response against cancer, and contributes to cancer cells aggressiveness. The aim of this study was to assess the role of monocyte activation, showed using three monoclonal antibodies against human CD64 (clones 22 and 32.2) and CD163 (clone Mac2-158), in differentiating patients with localized and metastatic BC. Patients and Methods: Sixteen women (median age 47 years, range 32-76 years) with confirmed invasive ductal carcinoma and positive axillary lymph nodes (pN1) who were not currently receiving chemotherapy (cases), and 18 age- and pT-matched pN0 women (controls) were enrolled in the study. The absolute neutrophil and monocyte count was obtained with routine hematological assay, while polymorphonuclear (PMN) CD64 index, monocyte CD64 index (as direct marker of monocyte activation), and monocyte CD163 index were assayed using a specific commercial kit. Each sample (50 μL) was prepared and analyzed by flow cytometry, according to the manufacturer's guidelines. Results: The absolute neutrophil and monocyte counts did not differ (p=NS) between groups (cases vs. controls), as well as PMC CD64 index (7.5±2.3 vs. 8.5±2.1, p=0.19). The monocyte CD64 index was significantly higher in patients with metastatic BC (10.5±2.1 vs. 8.4±1.9, p=0.004), while monocyte CD163 index was lower (2451±256 vs. 2711±365, p=0.024). Conclusions: Usually, PMN CD64 index increases during infections in response to specific cytokines. An elevated monocyte CD64 index suggests that monocyte vs. neutrophil activation may have a role in mediating the response to the presence of metastases, while a lower monocyte CD163 index suggests a scavenger receptor shedding during monocyte activation. These preliminary data confirm the usefulness of monocyte activation markers measurement in patients with metastatic BC.Pubblicazioni consigliate
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