title: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Human Pathology, Wakayama Medical University, Kimiidera, Wakayama Japan.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Liu
authors.forename: Kennichi
authors.initials: K
authors.lastname: Kakudo
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Bai
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Li
authors.forename: Takashi
authors.initials: T
authors.lastname: Ozaki
authors.forename: Akira
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Emiko
authors.initials: E
authors.lastname: Taniguchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Mori
mesh_terms: D000328:Adult; D000368:Aged; D015820:Cadherins / Q000378:metabolism; D002277:Carcinoma; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D016764:Cell Polarity / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism; D011379:Prognosis; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D014746:Vimentin; D051176:beta Catenin