Expression of cancer-associated fibroblast-related proteins in thyroid papillary carcinoma

Woo Young Sun; Woo Hee Jung; Ja Seung Koo

doi:10.1007/s13277-015-4684-4

Expression of cancer-associated fibroblast-related proteins in thyroid papillary carcinoma

Woo Young Sun, Woo Hee Jung, Ja Seung Koo

Department of Pathology

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

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.

Original language	English
Pages (from-to)	8197-8207
Number of pages	11
Journal	Tumor Biology
Volume	37
Issue number	6
DOIs	https://doi.org/10.1007/s13277-015-4684-4
Publication status	Published - 2016 Jun 1

Bibliographical note

Funding Information:
This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, and Republic of Korea (1420080). This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2015R1A1A1A05001209)

Publisher Copyright:
© 2015, International Society of Oncology and BioMarkers (ISOBM).

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Medicine(all)

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10.1007/s13277-015-4684-4

Cite this

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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.",

author = "Sun, {Woo Young} and Jung, {Woo Hee} and Koo, {Ja Seung}",

note = "Funding Information: This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, and Republic of Korea (1420080). This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2015R1A1A1A05001209) Publisher Copyright: {\textcopyright} 2015, International Society of Oncology and BioMarkers (ISOBM).",

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doi = "10.1007/s13277-015-4684-4",

language = "English",

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T1 - Expression of cancer-associated fibroblast-related proteins in thyroid papillary carcinoma

AU - Sun, Woo Young

AU - Jung, Woo Hee

AU - Koo, Ja Seung

N1 - Funding Information: This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, and Republic of Korea (1420080). This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2015R1A1A1A05001209) Publisher Copyright: © 2015, International Society of Oncology and BioMarkers (ISOBM).

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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.

AB - 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.

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Expression of cancer-associated fibroblast-related proteins in thyroid papillary carcinoma

Abstract

Bibliographical note

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