Paired Related Homeobox 1 (PRRX1) Is Associated with Epithelial-Mesenchymal Transition (EMT) in Thyroid Tumors

Background: PRRX1 is a newly identifi ed transcription factor that induces EMT in various neoplasms. We examined the expression of PRRX1 in benign thyroid tissues and thyroid carcinomas and in a cultured thyroid cell line, PTC1, after induction of EMT with TGF1. Design: Anaplastic thyroid carcinomas (ATC, n=35), poorly differentiated thyroid carcinomas (n=21), papillary thyroid carcinomas (PTC, n=58), follicular carcinomas (n=28), follicular adenomas (n=32), nodular goiters (n=10) and normal thyroids (n=10) were analyzed by immunohistochemistry (IHC) using formalin-fi xed paraffi n-embedded tissue microarrays (TMAs). IHC was scored based on the percentage and intensity of stained cells. The association of PRRX1 expression with clinical features and prognostic factors was also analyzed. Whole sections of PTCs (n=20) were also analyzed by IHC for PRRX1 expression. The TPC1 cell line was treated with TGF1 to induce EMT and PRRX1 was analyzed by qRT-PCR. Results: PRRX1 showed nuclear expression mostly in ATCs (54%) in the TMAs compared to all other groups (p<0.005).Whole sections of PTCs were positive in 2/5 (40%) cases of the hobnail variant of PTCs while conventional PTCs (n=10) and tall cell variant of PTC (n=5) were all negative. Positive expression of PRRX1 correlated with patient age, lymph node metastasis, tumor size and extrathyroidal extension. Moreover PRRX1 was related to poorer survival in patients with thyroid cancer. After TGF1 induction of EMT, there was a 10 to 20 fold increase in PRRX1 mRNA expression over a 30 day period. Conclusions: The PRRX1 transcription factor is expressed mainly in ATC and in some aggressive variants of PTCs such as the hobnail variant in primary thyroid tumors. Induction of EMT in vitro by TGF1 treatment leads to increased expression of PRRX1.