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. 2008 Dec;15(4):1069-74.
doi: 10.1677/ERC-08-0036. Epub 2008 Aug 21.

Increased density of tumor-associated macrophages is associated with decreased survival in advanced thyroid cancer

Mabel Ryder  1 , Ronald A Ghossein, Julio C M Ricarte-Filho, Jeffrey A Knauf, James A Fagin
Affiliations

Increased density of tumor-associated macrophages is associated with decreased survival in advanced thyroid cancer

Mabel Ryder et al. Endocr Relat Cancer. 2008 Dec.

Abstract

Thyroid cancers are infiltrated with tumor-associated macrophages (TAMs), yet their role in cancer progression is not known. The objectives of this study were to characterize the density of TAMs in well-differentiated (WDTC), poorly differentiated (PDTC), and anaplastic thyroid cancers (ATC) and to correlate TAM density with clinicopathologic parameters. Immunohistochemistry was performed on tissue microarray sections from WDTC (n=33), PDTC (n=37), and ATC (n=20) using macrophage-specific markers. Electronic medical records were used to gather clinical and pathologic data. Follow-up information of PDTC patients was available for 0-12 years. In total, 9 out of 33 WDTC (27%), 20 out of 37 PDTC (54%), and 19 out of 20 ATC (95%) had an increased density of CD68(+) TAMs (> or = 10 per 0.28 mm(2); WDTC versus PDTC, P=0.03; WDTC versus ATC, P<0.0001; PDTC versus ATC, P<0.002). Increased TAMs in PDTC was associated with capsular invasion (P=0.034), extrathyroidal extension (P=0.009), and decreased cancer-related survival (P=0.009) compared with PDTC with a low density of TAMs. In conclusion, the density of TAMs is increased in advanced thyroid cancers. The presence of a high density of TAMs in PDTC correlates with invasion and decreased cancer-related survival. These results suggest that TAMs may facilitate tumor progression. As novel therapies directed against thyroid tumor cell-specific targets are being tested, the potential role of TAMs as potential modulators of the thyroid cancer behavior will need to be considered.

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Figures

Figure 1
Figure 1
Immunostain for tumor-associated macrophages (TAM) markers in tissue microarrays. The signal is golden brown. A: Very low density of CD68 + TAM per tissue core (0.28mm2) in well differentiated papillary carcinoma, follicular variant B: High power of A (arrow indicates isolated TAM). C: Moderate density of CD68 + TAM in poorly differentiated thyroid carcinomas. D: High power of C (arrow indicates TAM). E: Very high density of CD68 + TAM in anaplastic carcinoma. F: High power of E (arrow points to CD68 negative anaplastic bizarre carcinoma cell surrounded by TAM). G: Same case as E,F showing very high density of CD163 + TAM. H. High power of G (arrow points to CD163 negative anaplastic bizarre carcinoma cell surrounded by TAM).
Figure 2
Figure 2
Top: Kaplan-Meier log-rank cancer-related survival analyses of PDTC patients with or without increased TAMs (p=0.009). Bottom: Kaplan-Meier curve for patients with and without ETE at initial surgical presentation (p=0.005)
See this image and copyright information in PMC

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