title: MUC1 expression in papillary thyroid carcinoma is associated with BRAF mutation and lymph node metastasis; the latter is the most important risk factor of relapse.
abstract: BACKGROUND
  The incidence of papillary thyroid carcinoma (PTC) has increased over the past 30 years in Western countries. PTC is usually associated with a good prognosis, but there is a wide range of aggressiveness, and some patients develop distant metastasis and/or resistance to standard treatment. Early identification of these high-risk tumors is a current challenge for appropriate patient management. MUC1 expression has been studied previously in thyroid cancer, but its prognostic value remains controversial. Here, we correlated MUC1 expression in PTC with clinical and pathological features and with the presence of the BRAF(V600E) mutation.
  
  
  METHODS
  We performed a clinical and morphological analysis of 190 thyroid tumors (95 PTCs and 95 adenomas). MUC1 immunohistochemistry was carried out on a tissue microarray using different antibodies. The presence of the BRAF(V600E) mutation was investigated by pyrosequencing. MUC1 mRNA levels were assessed by quantitative reverse transcription polymerase chain reaction on a subset of PTC.
  
  
  RESULTS
  MUC1 expression was observed in 49% of PTCs and was found to correlate with the presence of papillary architecture, a stromal lymphoid infiltrate, aggressive histological subtypes, extrathyroidal extension, lymph node metastasis, nuclear pseudoinclusions, lymphovascular invasion, and the presence of the BRAF(V600E) mutation (p<0.0001). MUC1 was abundant in nuclear pseudoinclusions. Multivariate analysis showed a strong association of MUC1 expression with the presence of the BRAF(V600E) mutation and lymph node metastasis (p<0.0001). Lymph node metastasis was the most important risk factor of relapse.
  
  
  CONCLUSIONS
  Our study shows an association between MUC1 expression and the presence of the BRAF(V600E) mutation in PTC. Analysis of MUC1 expression could improve the risk stratification of PTCs.
authors.affiliation: 1 Institute of Pathology, Lille University Hospital , Lille, France .
authors.forename: Florence
authors.initials: F
authors.lastname: Renaud
authors.forename: Viviane
authors.initials: V
authors.lastname: Gnemmi
authors.forename: Patrick
authors.initials: P
authors.lastname: Devos
authors.forename: Sébastien
authors.initials: S
authors.lastname: Aubert
authors.forename: Michel
authors.initials: M
authors.lastname: Crépin
authors.forename: Lucie
authors.initials: L
authors.lastname: Coppin
authors.forename: Nassima
authors.initials: N
authors.lastname: Ramdane
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bouchindhomme
authors.forename: Michelle
authors.initials: M
authors.lastname: d'Herbomez
authors.forename: Isabelle
authors.initials: I
authors.lastname: Van Seuningen
authors.forename: Christine
authors.initials: C
authors.lastname: Do Cao
authors.forename: François
authors.initials: F
authors.lastname: Pattou
authors.forename: Bruno
authors.initials: B
authors.lastname: Carnaille
authors.forename: Pascal
authors.initials: P
authors.lastname: Pigny
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Wémeau
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Leteurtre
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism*; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf