The Significance of TROP2 Expression in Predicting Mutations in Papillary Thyroid Carcinoma.

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. mutations are the most common genetic alteration in papillary thyroid carcinoma (PTC). We evaluated the correlation between TROP2 expression and mutation in PTC.

Methods: First, we carried out pyrosequencing for 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 mutation. Second, we tested TROP2 mRNA expression in three thyroid cancer cell lines with 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 V600E mutation.

Results: In this study, 21 of 26 cases with mutation showed TROP2 immunoreactivity, whereas all 26 cases without 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 V600E mutation.

Conclusions: Based on these results, we concluded that TROP2 expression is significantly associated with mutation and that TROP2 immunohistochemistry could be used for predicting mutations or diagnosing papillary thyroid carcinoma.