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JPTM > Volume 52(1); 2018 > Article
Journal of Pathology and Translational Medicine 2018;52(1): 14-20.
doi: https://doi.org/10.4132/jptm.2017.10.17
The Significance of TROP2 Expression in Predicting BRAF Mutations in Papillary Thyroid Carcinoma
Joon Seog Kong1 , Hyeon Jin Kim2 , Min-Jung Kim2, Areumnuri Kim2 , Dalnim Lee2 , Kanghee Han1 , Sunhoo Park1,2 , Jae Soo Koh1 , Jae Kyung Myung1,2
1Department of Pathology, Korea Cancer Center Hospital, Seoul, Korea
2Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
Corresponding Author: Jae Kyung Myung ,Tel: +82-2-970-1257, Fax: +82-2-970-2430, Email: tontos016@naver.com
Received: August 4, 2017;  Revised: October 8, 2017  Accepted: October 16, 2017.  Published online: December 11, 2017.
ABSTRACT

Background:
Trophoblast antigen 2 (TROP2) is a human trophoblast cell-surface glycoprotein that is overexpressed in several types of epithelial cancers, and is suggested to be associated with an unfavorable prognosis. BRAF mutations are the most common genetic alteration in papillary thyroid carcinoma (PTC). We evaluated the correlation between TROP2 expression and BRAF mutation in PTC.
Methods:
First, we carried out pyrosequencing for BRAF mutations and immunohistochemistry for TROP2 expression with a tissue microarray consisting of 52 PTC cases. Membranous staining in at least 5% of tumor cells was designated as positive staining and we analyzed the relationship between TROP2 expression and diverse clinicopathological factors, including BRAF mutation. Second, we tested TROP2 mRNA expression in three thyroid cancer cell lines with BRAF mutations (BCPAP, SNU790, and 8505C) and a normal thyroid cell line. Additionally, we checked TROP2 protein levels in a normal thyroid cell line after introduction of the BRAF V600E mutation.
Results:
In this study, 21 of 26 cases with BRAF mutation showed TROP2 immunoreactivity, whereas all 26 cases without BRAF mutation showed no immunoreactivity for TROP2 with a statistically significant difference (p<.001). Upregulation of TROP2 mRNA was observed in all three thyroid cancer cell lines, but not in the normal thyroid cell line. Interestingly, however, the TROP2 expression was increased in the normal thyroid cell line after introduction of the BRAF V600E mutation.
Conclusions:
Based on these results, we concluded that TROP2 expression is significantly associated with BRAF mutation and that TROP2 immunohistochemistry could be used for predicting BRAF mutations or diagnosing papillary thyroid carcinoma.
Key Words: TROP2; BRAF mutation; Papillary thyroid carcinoma