Stromal macrophage expressing CD204 is associated with tumor aggressiveness in lung adenocarcinoma.
BACKGROUND
Tumor tissue is composed of variable numbers of cancer cells and stromal cells, and tumor-associated macrophages are recruited into cancer-induced stroma and produce a specific microenvironment. Alternatively, activated macrophages (M2 phenotype) are known to be related to tumor progression and outcome, and CD204 has been reported to be expressed in M2 macrophages in some tumors.


METHODS
To investigate whether CD204-positive macrophages reflect tumor aggressiveness in adenocarcinoma of the lung, we investigated the relationships between the numbers of CD204-positive stromal macrophages and both clinicopathological features and outcome in 170 consecutive resected cases. We also examined the relationships between the numbers of CD204-positive macrophages and the expression levels of cytokines involved in the migration and differentiation of M2 macrophages.


RESULTS
The numbers of CD204-positive macrophages were significantly correlated with several prognostic factors. The log-rank test showed a significant association between the numbers of CD204-positive macrophages and a poor outcome (p = 0.0073), whereas the numbers of macrophages expressing CD68, a pan-macrophage/monocyte marker, were of marginal prognostic significance (p = 0.0789). We evaluated associations between the levels of expression of the cytokines IL-6, IL-10, IL-12a, IL-12b, M-colony-stimulating factor, IFN-gamma-., and monocyte chemoattractant protein-1 in cancer tissue and the numbers of CD204-positive macrophages. The expression levels of IL-10 and monocyte chemoattractant protein-1, which are involved in differentiation, accumulation, and migration of M2 macrophages, were significantly correlated with the numbers of CD204-positive macrophages (p = 0.031 and p = 0.031, respectively).


CONCLUSIONS
These findings demonstrated that CD204-positive macrophages clearly reflect the tumor-promoting phenotype of tumor-associated macrophages in lung adenocarcinoma.
Ohtaki
Yoichi
Y
Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Ishii
Genichiro
G
Nagai
Kanji
K
Ashimine
Satoshi
S
Kuwata
Takeshi
T
Hishida
Tomoyuki
T
Nishimura
Mitsuyo
M
Yoshida
Junji
J
Takeyoshi
Izumi
I
Ochiai
Atsushi
A
D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D051117:Scavenger Receptors, Class A / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism*
D014408:Biomarkers, Tumor; D016207:Cytokines; C495139:MSR1 protein, human; D051117:Scavenger Receptors, Class A