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

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.