Density of Tumor-associated Macrophages Correlates with Lymph Node Metastasis in Papillary Thyroid Carcinoma

Overview

Journal Thyroid

Date 2012 Aug 9

PMID 22870901

Citations 79

Authors

Wei Qing

Wei-Yuan Fang

Lei Ye

Li-Yun Shen

Xiao-Fang Zhang

Xiao-Chun Fei

Xi Chen

Wei-Qing Wang

Xiao-Ying Li

Jia-Cheng Xiao

Guang Ning

Affiliations

Soon will be listed here.

Abstract

Background: Tumor-associated macrophages (TAMs) have recently been recognized as being important players in the tumoriogenesis of many cancers, including advanced thyroid cancer. However, a role in papillary thyroid carcinoma (PTC), the most prevalent thyroid cancer, has not been established. We hypothesized that TAMs also facilitate tumor progression in PTC.

Methods: We investigated TAMs density in both benign thyroid lesions and PTC tumors by CD68 immunostaining. CD68-positive cell density was further associated with the clinicopathological characteristics of PTC patients. Finally, TAMs were isolated from PTC tumors and phenotyped by cytokine and receptor profiling.

Results: The overall density of TAMs was found to be significantly higher in PTC tumors, compared with thyroid goiter and follicular adenoma. The density of TAMs was positively associated with lymph node metastasis in TNM (tumor-node-metastasis) stages III/VI compared with stages I/II. No association was observed in other common tumor features, including the BRAF mutation. The isolated TAMs presented with high levels of M2-associated cytokine and receptors, making M2 the predominant TAM phenotype.

Conclusions: TAMs may play a functional role in the progression of PTC.

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References

Caillou B, Talbot M, Weyemi U, Pioche-Durieu C, Al Ghuzlan A, Bidart J . Tumor-associated macrophages (TAMs) form an interconnected cellular supportive network in anaplastic thyroid carcinoma. PLoS One. 2011; 6(7):e22567. PMC: 3141071. DOI: 10.1371/journal.pone.0022567. View

Fiumara A, Belfiore A, Russo G, Salomone E, Santonocito G, Ippolito O . In situ evidence of neoplastic cell phagocytosis by macrophages in papillary thyroid cancer. J Clin Endocrinol Metab. 1997; 82(5):1615-20. DOI: 10.1210/jcem.82.5.3909. View

Qian B, Pollard J . Macrophage diversity enhances tumor progression and metastasis. Cell. 2010; 141(1):39-51. PMC: 4994190. DOI: 10.1016/j.cell.2010.03.014. View

Mukhtar R, Moore A, Nseyo O, Baehner F, Au A, Moore D . Elevated PCNA+ tumor-associated macrophages in breast cancer are associated with early recurrence and non-Caucasian ethnicity. Breast Cancer Res Treat. 2011; 130(2):635-44. DOI: 10.1007/s10549-011-1646-4. View

Mazzaferri E, Jhiang S . Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med. 1994; 97(5):418-28. DOI: 10.1016/0002-9343(94)90321-2. View

Biswas S, Gangi L, Paul S, Schioppa T, Saccani A, Sironi M . A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood. 2005; 107(5):2112-22. DOI: 10.1182/blood-2005-01-0428. View

Sherman S, Brierley J, Sperling M, Ain K, Bigos S, Cooper D . Prospective multicenter study of thyroiscarcinoma treatment: initial analysis of staging and outcome. National Thyroid Cancer Treatment Cooperative Study Registry Group. Cancer. 1998; 83(5):1012-21. DOI: 10.1002/(sici)1097-0142(19980901)83:5<1012::aid-cncr28>3.0.co;2-9. View

Xing M . Prognostic utility of BRAF mutation in papillary thyroid cancer. Mol Cell Endocrinol. 2009; 321(1):86-93. PMC: 2849928. DOI: 10.1016/j.mce.2009.10.012. View

Sica A, Saccani A, Bottazzi B, Polentarutti N, Vecchi A, Van Damme J . Autocrine production of IL-10 mediates defective IL-12 production and NF-kappa B activation in tumor-associated macrophages. J Immunol. 2000; 164(2):762-7. DOI: 10.4049/jimmunol.164.2.762. View

10.

Solinas G, Schiarea S, Liguori M, Fabbri M, Pesce S, Zammataro L . Tumor-conditioned macrophages secrete migration-stimulating factor: a new marker for M2-polarization, influencing tumor cell motility. J Immunol. 2010; 185(1):642-52. DOI: 10.4049/jimmunol.1000413. View

11.

Kim D, Min H, Lee K, Kim Y, Oh D, Jeon Y . High tumour islet macrophage infiltration correlates with improved patient survival but not with EGFR mutations, gene copy number or protein expression in resected non-small cell lung cancer. Br J Cancer. 2008; 98(6):1118-24. PMC: 2275476. DOI: 10.1038/sj.bjc.6604256. View

12.

Davies L, Welch H . Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA. 2006; 295(18):2164-7. DOI: 10.1001/jama.295.18.2164. View

13.

DeGroot L, Kaplan E, McCormick M, STRAUS F . Natural history, treatment, and course of papillary thyroid carcinoma. J Clin Endocrinol Metab. 1990; 71(2):414-24. DOI: 10.1210/jcem-71-2-414. View

14.

Mazzaferri E, Kloos R . Clinical review 128: Current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab. 2001; 86(4):1447-63. DOI: 10.1210/jcem.86.4.7407. View

15.

Ryder M, Ghossein R, Ricarte-Filho J, Knauf J, Fagin J . Increased density of tumor-associated macrophages is associated with decreased survival in advanced thyroid cancer. Endocr Relat Cancer. 2008; 15(4):1069-74. PMC: 2648614. DOI: 10.1677/ERC-08-0036. View

16.

Leboulleux S, Rubino C, Baudin E, Caillou B, Hartl D, Bidart J . Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis. J Clin Endocrinol Metab. 2005; 90(10):5723-9. DOI: 10.1210/jc.2005-0285. View

17.

Duff M, Mestre J, Maddali S, Yan Z, Stapleton P, Daly J . Analysis of gene expression in the tumor-associated macrophage. J Surg Res. 2007; 142(1):119-28. DOI: 10.1016/j.jss.2006.12.542. View

18.

Buechler C, Ritter M, Orso E, Langmann T, Klucken J, Schmitz G . Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro- and antiinflammatory stimuli. J Leukoc Biol. 2000; 67(1):97-103. View

19.

Elisei R, Molinaro E, Agate L, Bottici V, Masserini L, Ceccarelli C . Are the clinical and pathological features of differentiated thyroid carcinoma really changed over the last 35 years? Study on 4187 patients from a single Italian institution to answer this question. J Clin Endocrinol Metab. 2010; 95(4):1516-27. DOI: 10.1210/jc.2009-1536. View

20.

Lewis C, Leek R, Harris A, Mcgee J . Cytokine regulation of angiogenesis in breast cancer: the role of tumor-associated macrophages. J Leukoc Biol. 1995; 57(5):747-51. DOI: 10.1002/jlb.57.5.747. View