Tumor-Associated CD204-Positive Macrophage Is a Prognostic Marker in Clinical Stage I Lung Adenocarcinoma

Abstract

Objective: Macrophages are the dominant leukocytes in the tumor microenvironment. Accumulating evidence revealed that CD204-positive (CD204+) tumor-associated macrophages (TAMs) are associated with the aggressive behavior of various cancers; however, the clinical, pathological, and prognostic associations of CD204+ TAMs with the subtype of lung adenocarcinoma have not been reported.

Methods: Tissue microarray and immunohistochemistry were constructed from clinical stage I lung adenocarcinomas with radical surgical resection. The intratumoral density of CD204+ cells was calculated using image analysis software for analyses. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional hazards regression models.

Results: The intratumoral density of CD204 was correlated with T stage, nodal involvement, lymphovascular invasion, and cancer relapse after the surgery, but not with age, gender, or smoking history. The density of CD204 in non-LPD was significantly higher than that in LPD. The 5-year disease-free survival (DFS) rate of CD204 high-density group was significantly worse than that of CD204 low-density group.

Conclusions: The expression of CD204 in TAMs is associated with the aggressiveness of lung adenocarcinoma. Our results suggest that a specific immune microenvironment may be associated with the biological behavior of lung adenocarcinoma.

Figure 1

Quantitation of CD204 density in tissue microarray of stage I lung adenocarcinoma (a). Immunohistochemistry for CD204 shows low (b) and high (c) infiltration of CD204+ macrophages.

Figure 2

Percentages of tumor-infiltrating CD204+ macrophages in different subtypes of stage I lung adenocarcinoma.

Figure 3

Kaplan-Meier analysis of disease-free survival (a) and overall survival (b) of patients with lung adenocarcinoma according to CD204+ macrophage density.