Kong Joon Seog, Kim Hyeon Jin, Kim Min-Jung, Kim Areumnuri, Lee Dalnim, Han Kanghee, Park Sunhoo, Koh Jae Soo, Myung Jae Kyung
Department of Pathology, Korea Cancer Center Hospital, Seoul, Korea.
Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
J Pathol Transl Med. 2018 Jan;52(1):14-20. doi: 10.4132/jptm.2017.10.17. Epub 2017 Dec 11.
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.
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.
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.
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.
滋养层抗原2(TROP2)是一种人类滋养层细胞表面糖蛋白,在多种上皮癌中过度表达,提示其与不良预后相关。BRAF突变是甲状腺乳头状癌(PTC)中最常见的基因改变。我们评估了PTC中TROP2表达与BRAF突变之间的相关性。
首先,我们对52例PTC病例的组织芯片进行BRAF突变焦磷酸测序和TROP2表达免疫组化。至少5%肿瘤细胞的膜染色被指定为阳性染色,我们分析了TROP2表达与包括BRAF突变在内的多种临床病理因素之间的关系。其次,我们检测了三种携带BRAF突变的甲状腺癌细胞系(BCPAP、SNU790和8505C)和一种正常甲状腺细胞系中TROP2 mRNA的表达。此外,我们在导入BRAF V600E突变后检测了正常甲状腺细胞系中TROP2蛋白水平。
在本研究中,26例BRAF突变病例中有21例显示TROP2免疫反应性,而26例无BRAF突变病例均未显示TROP2免疫反应性,差异有统计学意义(p<0.001)。在所有三种甲状腺癌细胞系中均观察到TROP2 mRNA上调,但在正常甲状腺细胞系中未观察到。然而,有趣的是,导入BRAF V600E突变后,正常甲状腺细胞系中的TROP2表达增加。
基于这些结果,我们得出结论,TROP2表达与BRAF突变显著相关,TROP2免疫组化可用于预测BRAF突变或诊断甲状腺乳头状癌。