Loss of cellular polarity/cohesiveness in the invasive front of papillary thyroid carcinoma, a novel predictor for lymph node metastasis; possible morphological indicator of epithelial mesenchymal transition

Abstract

Background: Loss of cellular polarity/cohesiveness (LOP/C) in the invasive front of papillary thyroid carcinoma (PTC) results in a high recurrence risk of PTC.

Aims: To investigate the immunohistochemical features of LOP/C in PTC and to show that this feature is linked to a high association of lymph node metastasis (LNM) at surgery and tumour recurrence.

Methods: The degree of LOP/C of the PTCs was evaluated histologically using a cut-off value of 20% and the immunohistochemical features of LOP/C were analysed using immunohistochemical staining for E-cadherin, β-catenin and vimentin. The relationship between the LOP/C and the other clinicopathological parameters was analysed.

Results: 43 cases of PTC with LOP/C (≥20%) were selected and 27 cases with LOP/C (<20%) were included as control tumours. 11/44 cases (25%) were observed to develop recurrence, LNM or distant metastasis at an average follow-up of 31 months. Less expression of E-cadherin and aberrant localisation of β-catenin and vimentin were observed in PTC tumour cells with LOP/C. LOP/C (≥20%) was significantly correlated with extrathyroid invasion (r=0.336, p=0.003), advanced tumour stage (r=0.275, p=0.017), LNM (r=0.389, p<0.001) and recurrence after surgery (r=0.302, p=0.036). Both extrathyroid invasion and LOP/C were independent significant predictors of LNM.

Conclusions: LOP/C may be a useful morphological feature of epithelial mesenchymal transition under H&E observation, and it is an important indicator of lymph node metastasis and aggressive clinical behaviour of PTC.