Endocrinol Metab.  2016 Sep;31(3):469-475. 10.3803/EnM.2016.31.3.469.

Macrophage Densities Correlated with CXC Chemokine Receptor 4 Expression and Related with Poor Survival in Anaplastic Thyroid Cancer

• Kim DI
• Kim E
• Kim YA
• Cho SW
• Lim JA
• Park YJ

• KMID: 2352988
• DOI: http://doi.org/10.3803/EnM.2016.31.3.469

Abstract

BACKGROUND
Tumor associated macrophages (TAMs) and CXC chemokine receptor 4 (CXCR4) have emerged as potential biomarkers in various human cancers. The aims of this study were to investigate the clinical characteristics of anaplastic thyroid cancer (ATC) patients according to the TAM numbers in the tumor tissue, and to evaluate the associations between CXCR4 expressions and macrophage densities in ATC tumor microenvironment.
METHODS
Total 14 ATC samples from thyroid tissue microarray were used. Immunohistochemical staining was performed using anti-CD163 and anti-CXCR4 antibodies. According to the immunoreactivity of CD163, all subjects were divided into two groups: low-CD163 (n=8) and high-CD163 (n=6) groups.
RESULTS
The mean diagnostic age was 65±7 years and the median tumor size was 4.3 cm, ranging 2.5 to 15 cm. Clinicopathological characteristics were not significantly different between low-CD163 and high-CD163 groups, while age of diagnosis was younger in high-CD163 group than that of low-CD163 group with marginal significance (56.9±5.5 years vs. 67.5±6.8 years, P=0.09). However, overall survival was significantly reduced in high-CD163 group (5.5 months [range, 1 to 10]) compared with low-CD163 groups (8.8 months [range, 6 to 121); log-rank test, P=0.0443). Moreover, high-CD163 group showed strong CXCR4 expressions in both cancer and stromal compartments, while low-CD163 group showed relatively weak, stromal-dominant CXCR4 expressions. Additionally, CD163 and CXCR4 expressions showed a strong positive correlation (γ²=0.432, P=0.013).
CONCLUSION
Increased number of TAMs showed poor overall survival in ATC, suggesting TAMs are potentially a prognostic biomarker for ATC. CXCR4 expression was significantly correlated with CD163-positive TAM densities, which suggest the possible role of CXCR4 in TAM recruitments.

Keyword

Thyroid carcinoma, anaplastic; CD163; Tumor-associated macrophages; Receptors, CXCR4

MeSH Terms

Antibodies
Biomarkers
Diagnosis
Humans
Macrophages*
Receptors, CXCR*
Receptors, CXCR4*
Thyroid Carcinoma, Anaplastic*
Thyroid Gland
Tumor Microenvironment
Antibodies
Biomarkers
Receptors, CXCR
Receptors, CXCR4

Figure

• 

  Fig. 1 Kaplan-Meier curves for overall survival of anaplastic thyroid cancer patients groups according to tumor-associated macrophages density.

• 

  Fig. 2 Expressions of CXC chemokine receptor 4 (CXCR4) and CD163 in anaplastic thyroid cancer tissues. (A) Represent immunohistochemical staining images of CD163 and CXCR4. (B) Correlations between CD163 and CXCR4 expressions. DAB, 3,3'-diaminobenzidine.

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