Expression of the embryonic morphogen Nodal in differentiated thyroid carcinomas: Immunohistochemistry assay in tissue microarray and The Cancer Genome Atlas data analysis

Surgery. 2014 Dec;156(6):1559-67; discussion 1567-8. doi: 10.1016/j.surg.2014.08.050. Epub 2014 Nov 11.

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).

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Follicular / genetics*
  • Adenocarcinoma, Follicular / pathology
  • Adenoma / genetics
  • Adenoma / pathology
  • Biopsy, Needle
  • Carcinogenesis
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Carcinoma, Papillary
  • Confidence Intervals
  • DNA Mutational Analysis
  • Databases, Factual
  • Diagnosis, Differential
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genome-Wide Association Study
  • Goiter / genetics
  • Goiter / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Multivariate Analysis
  • Nodal Protein / genetics*
  • Odds Ratio
  • Proto-Oncogene Proteins B-raf / genetics*
  • RNA, Messenger / analysis
  • Sampling Studies
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology

Substances

  • Nodal Protein
  • RNA, Messenger
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf