title: Prognostic value of tumor-associated macrophages according to histologic locations and hormone receptor status in breast cancer.
abstract: Tumor-associated macrophages (TAMs) are involved in tumor progression by promoting epithelial-mesenchymal transition (EMT), tumor cell invasion, migration and angiogenesis. However, in breast cancer, the clinical relevance of the TAM infiltration according to distinct histologic locations (intratumoral vs. stromal) and hormone receptor status is unclear. We investigated the significance of the levels of TAM infiltration in distinct histologic locations in invasive breast cancer. We also examined the relationship of the TAM levels with the clinicopathologic features of tumors, expression of EMT markers, and clinical outcomes. Finally, we analyzed the prognostic value of TAM levels according to hormone receptor status. High levels of infiltration of intratumoral, stromal and total TAMs were associated with high histologic grade, p53 overexpression, high Ki-67 proliferation index and negative hormone receptor status. Infiltration of TAMs was also correlated with overexpression of vimentin, smooth muscle actin and alteration of β-catenin. Overall, a high level of infiltration of intratumoral TAMs was associated with poor disease-free survival, and was found to be an independent prognostic factor. In subgroup analyses by hormone receptor status, a high level of infiltration of intratumoral TAM was an independent prognostic factor in the hormone receptor-positive subgroup, but not in the hormone-receptor negative subgroup. Our findings suggest that intratumoral TAMs play an important role in tumor progression in breast cancer, especially in the hormone receptor-positive group, and the level of TAM infiltration may be used as a prognostic factor and even a therapeutic target in breast cancer.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Moon
authors.initials: JM
authors.lastname: Gwak
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Republic of Korea.
authors.forename: Min Hye
authors.initials: MH
authors.lastname: Jang
authors.affiliation: Green Cross Laboratory, Yongin, Gyeonggi, Republic of Korea.
authors.forename: Dong Il
authors.initials: DI
authors.lastname: Kim
authors.affiliation: Department of Pathology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: An Na
authors.initials: AN
authors.lastname: Seo
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Republic of Korea.
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Park
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; C067980:CD68 antigen, human; D000097382:CD68 Molecule