Prognostic implication of histological features associated with EHD2 expression in papillary thyroid carcinoma

Abstract

Papillary thyroid carcinoma (PTC) is a heterogeneous tumor with various histological and molecular subtypes. EHD2 is involved in endocytosis and endosomal recycling. This study aimed to investigate the prognostic significance of EHD2 expression in PTC and develop a new model for predicting persistent/recurrent disease after thyroidectomy. Pathologic slides of 512 consecutive patients with PTC ≥ 1 cm were retrospectively reviewed. BRAF mutation analysis and immunohistochemistry for EHD2 were performed. Clinical significance of EHD2 mRNA expression was analyzed in 388 PTC patients using The Cancer Genome Atlas dataset. The presence of dyscohesive cells and psammoma bodies were found have significant association with persistent/recurrent disease (p = 0.049 and p = 0.038, respectively). The best discrimination of disease-free survival was found by dividing patients into three prognostic groups based on the following two risk factors according to the size category: psammoma bodies ≥ 4 and dyscohesive cells (≥ 1% and ≥ 20% in PTCs of < 2.0 cm and ≥ 2.0 cm, respectively). In PTCs of ≥ 2.0 cm, patients with the two risk factors had a hazard ratio of 13.303 (p = 0.005) compared to those without risk factors. High expression level of EHD2 was associated with BRAF V600E (p < 0.001), presence of dyscohesive cells (p = 0.010), and absence of psammoma bodies (p = 0.001). Increased EHD2 mRNA expression level was associated with extrathyroidal extension (p < 0.001), pT3-4 (p < 0.001), lymph node metastasis (p < 0.001), higher risk of recurrence (p < 0.001), and BRAF V600E (p < 0.001). Our prognostic model is useful for predicting persistent/recurrent disease after surgery of PTC. EHD2 mRNA expression could be a novel prognostic marker for PTC patients.

EHD2 is a Predictive Biomarker of Chemotherapy Efficacy in Triple Negative Breast Carcinoma

“…Downregulation of EHD2 has been associated with poor prognosis in esophageal squamous cell carcinoma, hepatocellular carcinoma and breast cancer 4,7,9 . In contrast, EHD2 overexpression was associated with poor prognosis in thyroid carcinoma 26 . We found in our study that low EHD2 expression is associated with good prognosis of TNBC.…”

Serum MMP-2 as a potential predictive marker for papillary thyroid carcinoma

“…Although differentiated PTC carries a favorable prognosis, it causes a postoperative recurrence rate as high as 30% during long-term follow-up [ 3 ]. A few biomarkers have been identified for the diagnosis of PTC, including EHD2 [ 4 ], Notch signaling [ 5 ], HER-2/neu [ 6 ], and CXCL12 [ 7 ], without clear evidence of their efficacy for clinical use. Therefore, the identification and validation of reliable biomarkers for diagnostic and prognostic prediction of PTC is urgently needed in clinical work.…”

CD73 Overexpression Promotes Progression and Recurrence of Papillary Thyroid Carcinoma

“…We enrolled 511 patients who underwent surgery for PTC from January 2008 to December 2010. The present study was performed on the same cohort used in our previous studies [ 34 , 35 , 36 , 37 ]. However, the number of patients was different because tissue loss inevitably occurs during sectioning and staining of the same archival tissue blocks.…”

“…PCR reaction was performed using BRAF exon 15-specific primers (forward 5′-TCATAATGCTTGCTCTGATAGGA-3′ and reverse 5′-GGCCAAAAATTTAATCAGTGGA-3′). Bidirectional sequencing was performed using the same primers and BigDye Terminator sequencing kit (Applied Biosystems, Foster City, CA, USA; No.4337457 on a 3730xl DNA analyzer (Applied Biosystems)), as previously described [ 34 , 36 , 40 ].…”