High numbers of macrophages, especially M2-like (CD163-positive), correlate with hyaluronan accumulation and poor outcome in breast cancer.
OBJECTIVE
High amounts of tumour-associated macrophages (TAMs) and hyaluronan (HA) correlate with tumour aggressiveness in breast cancer, but the relationship between these parameters is unclear. The aim of this study was to assay the numbers of TAMs in 278 human breast cancer cases, and their correlations with HA-related factors, clinical variables, and outcome.


RESULTS
The immunoreactivities for CD163 and CD68 were considered as indicators for M2-like and all TAMs, respectively. The numbers of TAMs were counted in at least four hot spots, and averaged to represent the numbers of TAMs in each section. In the statistical analyses, the numbers were graded as either low or high according to the median. High numbers of TAMs correlated with a high tumour HA content, HA synthases, CD44 positivity, and poor outcome. The number of CD163-positive cells represented a strong independent prognostic factor. There was also a significant correlation between obesity and a high number of CD163-positive cells.


CONCLUSIONS
Concurrent increases in TAMs and HA in breast cancer indicate that the accumulation of HA facilitates macrophage infiltration and inflammatory responses during human breast cancer progression.
Department of Oncology, Cancer Centre, Kuopio University Hospital, Kuopio, Finland.
Satu
S
Tiainen
Ritva
R
Tumelius
Kirsi
K
Rilla
Kirsi
K
Hämäläinen
Markku
M
Tammi
Raija
R
Tammi
Veli-Matti
VM
Kosma
Sanna
S
Oikari
Päivi
P
Auvinen
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis / Q000378:metabolism; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000473:pathology*; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000032:analysis; D000098902:CD163 Antigen; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D006820:Hyaluronic Acid; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule
CD163; CD68; Hyaluronan; breast cancer; hyaluronan synthase; obesity; tumour-associated macrophage