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M Ryder, Endocrinology, Memorial Sloan-Kettering Cancer Center, New York, 10021, United States
R Ghossein, Pathology, Memorial Sloan-Kettering Cancer Center, New York, United States
J Ricarte-Filho, Endocrinology, Memorial Sloan-Kettering Cancer Center, New York, United States
J Knauf, Endocrinology, Memorial Sloan-Kettering Cancer Center, New York, United States
J Fagin, Endocrinology, Memorial Sloan-Kettering Cancer Center, New York, United States

Correspondence: Mabel Ryder, Email: ryderm{at}mskcc.org

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. Nine of 33 WDTC (27%), 20/37 PDTC (54%) and 19/20 ATC (95%) had an increased density of CD68+ TAMs (=/>10 per 0.28 mm2) (p = 0.03, WDTC vs. PDTC; p < 0.0001. WDTC vs. ATC; p < 0.002, PDTC vs. ATC). 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 to 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.