Ryder Mabel, Ghossein Ronald A, Ricarte-Filho Julio C M, Knauf Jeffrey A, Fagin James A
Endocrinology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 296, New York, New York 10021, USA.
Endocr Relat Cancer. 2008 Dec;15(4):1069-74. doi: 10.1677/ERC-08-0036. Epub 2008 Aug 21.
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.
甲状腺癌中浸润有肿瘤相关巨噬细胞(TAM),但其在癌症进展中的作用尚不清楚。本研究的目的是描述高分化(WDTC)、低分化(PDTC)和未分化甲状腺癌(ATC)中TAM的密度,并将TAM密度与临床病理参数相关联。使用巨噬细胞特异性标记物对来自WDTC(n = 33)、PDTC(n = 37)和ATC(n = 20)的组织微阵列切片进行免疫组织化学分析。利用电子病历收集临床和病理数据。PDTC患者的随访信息可得0至12年。总共,33例WDTC中有9例(27%)、37例PDTC中有20例(54%)、20例ATC中有19例(95%)的CD68(+) TAM密度增加(≥每0.28平方毫米10个;WDTC与PDTC相比,P = 0.03;WDTC与ATC相比,P < 0.0001;PDTC与ATC相比,P < 0.002)。与TAM密度低的PDTC相比,PDTC中TAM增加与包膜侵犯(P = 0.034)、甲状腺外侵犯(P = 0.009)及癌症相关生存率降低(P = 0.009)相关。总之,晚期甲状腺癌中TAM密度增加。PDTC中高密度TAM的存在与侵犯及癌症相关生存率降低相关。这些结果提示TAM可能促进肿瘤进展。随着针对甲状腺肿瘤细胞特异性靶点的新型疗法正在进行测试,需要考虑TAM作为甲状腺癌行为潜在调节因子的潜在作用。