title: Expression of cancer-associated fibroblast-related proteins in thyroid papillary carcinoma.
abstract: The purpose of this study was to evaluate the association between expression of cancer-associated fibroblast (CAF)-related proteins in papillary thyroid carcinoma (PTC) and clinicopathologic factors. Using tissue microarray (TMA) constructed from 339 cases of PTC (303 classic type, 36 follicular variant), we performed immunohistochemical staining for podoplanin, prolyl 4-hydroxylase, FAPα, S100A4, PDGFRα, PDGFRβ, NG2, 5-meC, and BRAF V600E and evaluated the association with clinicopathologic parameters. We classified the stroma of PTC as desmoplastic type, sclerotic type, pauci type, or inflammatory type. The expression of prolyl 4-hydroxylase (p = 0.042), FAPα (p = 0.044), PDGFRα (p < 0.001), and 5-meC (p = 0.030) in cancer cells differed according to the histologic subtype, higher in classic type than follicular type. The expression of FAPα (p = 0.034) and 5-meC (p = 0.021) in stromal cells was higher in the classic type than follicular type. PTC with BRAF mutation showed higher expression of podoplanin (p < 0.001), prolyl 4-hydroxylase (p = 0.013), FAPα (p < 0.001), S100A4 (p < 0.001), PDGFRα (p < 0.001), and 5-meC (p < 0.001) in the tumor cell compartment and of FAPα (p = 0.004), S100A4 (p < 0.001), PDGFRα (p = 0.002), PDGFRβ (p < 0.001), and 5-meC (p < 0.001) in the stromal cell compartment. There was also a difference in the expression of CAF-related proteins according to stromal phenotype; the expression of FAPα, S100A4, and PDGFRα was higher in desmoplastic type than in other subtypes, whereas NG2 expression was higher in inflammatory type (p < 0.001). Tumoral podoplanin negativity (p = 0.043) was associated with shorter DFS, and tumoral S100A4 positivity (p = 0.044) and stromal PDGFRβ positivity (p = 0.035) were associated with shorter OS. In conclusion, the expression of CAF-related proteins in cancer cells and stromal cells of PTC was different according to histologic subtype, BRAF V600E mutation, and subtype of stroma, and was related to prognosis.
authors.affiliation: Department of Surgery, Daejeon St. Mary's Hospital, The Cathololic University of Korea College of Medicine, Daejeon, Korea.
authors.forename: Woo-Young
authors.initials: WY
authors.lastname: Sun
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
authors.forename: Woo-Hee
authors.initials: WH
authors.lastname: Jung
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea. kjs1976@yuhs.ac.
authors.forename: Ja Seung
authors.initials: JS
authors.lastname: Koo
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D012189:Retrospective Studies; D017154:Stromal Cells / Q000378:metabolism*; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor
keywords: Cancer-associated fibroblast; Papillary carcinoma; Thyroid