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Expression of the membrane mucins MUC4 and MUC15, potential markers of malignancy and prognosis, in papillary thyroid carcinoma

 Kee-Hyun Nam  ;  Tae-Woong Noh  ;  So-Hyang Chung  ;  So Hee Lee  ;  Mi Kyung Lee  ;  Soon Won Hong  ;  Woong Youn Chung  ;  Eun Jig Lee  ;  Cheong Soo Park 
 THYROID, Vol.21(7) : 745-750, 2011 
Journal Title
Issue Date
Adult ; Biomarkers, Tumor/analysis* ; Carcinoma ; Carcinoma, Papillary/metabolism* ; Female ; Humans ; Male ; Middle Aged ; Mucin-4/biosynthesis* ; Mucins/biosynthesis* ; Prognosis ; Thyroid Neoplasms/metabolism*
BACKGROUND: Papillary thyroid carcinoma (PTC) is the most frequent carcinoma of the thyroid gland and has a relatively good prognosis. However, it is important to identify PTC characteristics that indicate high risk for recurrence and metastasis. To date, overexpression of the membrane mucin, MUC1, has been investigated as a key molecular event in the pathogenesis of aggressive PTC. However, other membrane-associated mucins, matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-13 (TIMP-3), have not been studied yet. The aim of this study was to evaluate the expression levels of MUC4, MUC15, MMP-13, and TIMP-3 and their prognostic significance in PTC. METHODS: We analyzed MUC4, MUC15, MMP-13, and TIMP-3 expression in 10 PTC and 10 normal thyroid tissue samples using real-time reverse transcription-polymerase chain reaction. Tissue array blocks were obtained from 98 PTC cases. Tumor regions and nontumor regions were analyzed in tissue array blocks and immunohistochemistry studies were conducted using sectioned slides. Semiquantitative scores were correlated with clinicopathological factors of 98 PTC patients. RESULTS: MUC4- and MUC15-specific mRNA was increased by 78-fold and 4.75-fold, respectively, in PTC samples compared with normal thyroid tissues. MMP-13 and TIMP-3 gene expression levels were decreased by approximately 0.39-fold and 0.53-fold, respectively. By immunohistochemistry, MUC4 and MUC15 expression levels were increased in PTC samples compared with normal thyroid tissues (p < 0.001). MMP-13 and TIMP-3 expression levels were decreased in PTC samples compared with normal thyroid tissues (p < 0.001). High MUC4 scores were significantly correlated with small tumor size and papillary thyroid microcarcinoma subtype. High MUC15 scores were significantly correlated with age (≥45 years), distant metastasis, and multifocality. CONCLUSIONS: MUC4 and MUC15 were overexpressed in PTC, and high MUC15 expression was associated with high malignant potential. MUC15 may serve as a prognostic marker and potential novel therapeutic target in PTC.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Nam, Kee Hyun(남기현) ORCID logo https://orcid.org/0000-0002-6852-1190
Noh, Tae Woong(노태웅)
Park, Cheong Soo(박정수)
Lee, So Hee(이소희)
Lee, Eun Jig(이은직) ORCID logo https://orcid.org/0000-0002-9876-8370
Chung, Woung Youn(정웅윤)
Hong, Soon Won(홍순원) ORCID logo https://orcid.org/0000-0002-0324-2414
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