title: Expression of decoy receptor 3 in diffuse sclerosing variant of papillary thyroid carcinoma: correlation with M2 macrophage differentiation and lymphatic invasion.
abstract: BACKGROUND
  The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a unique variant of PTC that is characterized by extensive lymphovascular invasion of tumor cells in a background of lymphocytic thyroiditis. The lymphatic emboli contain tumor cells as well as macrophages, but the recruitment of these macrophages is not well understood. The aim of this study was to determine the relationship between the expression of Decoy receptor 3 (DcR3), the recruitment of tumor-associated macrophages (TAMs), and lymphatic invasion in DSV-PTC.
  
  
  METHODS
  We retrospectively examined 14 cases of DSV-PTC using immunohistochemistry studies. The density of TAMs, lymphatic vessel density, lymphatic invasion, tumor emboli area, and DcR3 expression were assessed. Statistical analyses were performed using Fisher's exact test, unpaired t-test, and linear regression.
  
  
  RESULTS
  The lymphatic tumor emboli contained a relatively higher density of TAMs than stroma and classical PTC (CPTC) areas. In addition, the number of lymphatic invasions and the size of the tumor emboli area were positively correlated with the number of M2 TAMs. A higher density of M2 TAMs was associated with older patients and larger tumor size. Moreover, DcR3 was expressed only in lymphatic tumor cells and squamous metaplastic tumor cells, but not in macrophages and CPTC. In addition, the preferential expression of DcR3 in tumors was associated with higher levels of M2 TAMs and lymphatic invasion.
  
  
  CONCLUSIONS
  Despite the fact that the exact relationship between DcR3, M2 macrophages, and lymphatic invasion in DSV-PTC remains to be elucidated, our findings suggest that DcR3 expression in DSV-PTC tumor cells may promote the polarized macrophage differentiation toward the M2 phenotype. This phenomenon may further promote lymphatic invasion of DSV-PTC tumor cells.
authors.affiliation: Department of Pathology, Mackay Medicine, Nursing, and Management College, New Taipei City, Taiwan.
authors.forename: Wei-Chin
authors.initials: WC
authors.lastname: Chang
authors.forename: Jui-Yu
authors.initials: JY
authors.lastname: Chen
authors.forename: Chen-Hsen
authors.initials: CH
authors.lastname: Lee
authors.forename: An-Hang
authors.initials: AH
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002277:Carcinoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002291:Carcinoma, Papillary / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D002454:Cell Differentiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000378:metabolism*; D012189:Retrospective Studies; D012598:Sclerosis; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D047368:Tumor Burden
chemical_list: D009363:Neoplasm Proteins; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human