title: Expression of the embryonic morphogen Nodal in differentiated thyroid carcinomas: Immunohistochemistry assay in tissue microarray and The Cancer Genome Atlas data analysis.
abstract: BACKGROUND
  Nodal, an embryonic morphogen, plays a role in tumorigenesis of melanoma, breast, and prostate cancer; however, its role in thyroid carcinoma is unknown. We examined Nodal expression in thyroid tumors by immunohistochemistry assay and The Cancer Genome Atlas (TCGA) analysis.
  
  
  METHODS
  An immunohistochemistry assay was performed in a tissue microarray comprising 128 classic papillary thyroid carcinomas (PTC), 58 follicular thyroid carcinomas (FTC), 19 follicular variants of PTC (FVPTC), 57 follicular adenomas (FA), 54 adenomatous goiters (AG), and 5 normal thyroid tissues. The TCGA database was examined to evaluate the expression of Nodal mRNA in normal thyroid and PTC.
  
  
  RESULTS
  The proportion of tumors showing negative Nodal expression in PTC, FTC, FVPTC, FA, and AG was 0%, 1.7%, 0%, 14%, and 41%, respectively. For the diagnosis of malignant tumors, the sensitivity, specificity, positive predictive value, and negative predictive value of positive Nodal staining was 99%, 27%, 72%, and 97%, respectively. High Nodal expression was associated with older age and BRAF mutation in PTC. TCGA analysis revealed PTC had greater Nodal mRNA expression than normal thyroid (P = .012).
  
  
  CONCLUSIONS
  Nodal staining might be useful "rule-out test" for the diagnosis of malignant thyroid tumor. Nodal may be associated with the tumorigenesis of thyroid malignancy.
authors.affiliation: Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea; Department of Surgery, Seoul National University Boramae Medical Center, Seoul, Korea.
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Chai
authors.affiliation: Department of Pathology, Seoul National University Boramae Medical Center, Seoul, Korea.
authors.forename: Young A
authors.initials: YA
authors.lastname: Kim
authors.affiliation: Research Institute, National Medical Center, Seoul, Korea.
authors.forename: Hyeon-Gun
authors.initials: HG
authors.lastname: Jee
authors.affiliation: Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea.
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Yi
authors.affiliation: Department of Pathology, Seoul National University Hospital and College of Medicine, Seoul, Korea.
authors.forename: Bo Gun
authors.initials: BG
authors.lastname: Jang
authors.affiliation: Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea. Electronic address: kyu.eun.lee.md@gmail.com.
authors.forename: Kyu Eun
authors.initials: KE
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital and College of Medicine, Seoul, Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea.
authors.forename: Yeo-Kyu
authors.initials: YK
authors.lastname: Youn
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000473:pathology; D001707:Biopsy, Needle; D063646:Carcinogenesis; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D016001:Confidence Intervals; D004252:DNA Mutational Analysis; D016208:Databases, Factual; D003937:Diagnosis, Differential; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006042:Goiter / Q000235:genetics / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D015999:Multivariate Analysis; D055457:Nodal Protein / Q000235:genetics*; D016017:Odds Ratio; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012494:Sampling Studies; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D055457:Nodal Protein; D012333:RNA, Messenger; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf