Defining the value of CD56, CK19, Galectin 3 and HBME-1 in diagnosis of follicular cell derived lesions of thyroid with systematic review of literature

Diagn Pathol. 2015 Oct 26:10:196. doi: 10.1186/s13000-015-0428-4.


Background: Nodular follicular lesions of thyroid gland comprise benign and malignant neoplasms, as well as some forms of hyperplasia. "Follicular" refers to origin of cells and in the same time to growth pattern - building follicles. Nodular follicular thyroid lesions have in common many morphological features, therefore attempts were made to define additional criteria for distinction between follicular adenoma, follicular carcinoma and follicular variant of papillary carcinoma. Increasing number of immunohistochemical markers is in the continual process of evaluation.

Methods: Tissue microarrays incorporating, total 201 cases, out of which 122 malignant and 79 benign follicular lesions, including neoplastic and non-neoplastic, were constructed and immunostained with antibodies to CD56, CK19, Galectin-3, HBME-1. Tissue cores were exclusively being acquired from tumour/lesion on interface with normal thyroid tissue. A systematic review of literature was done for period from the year 2001 to present time.

Results: All analysed markers may make a difference between benign lesions/tumours from differentiated thyroid carcinomas (p = <0.01, for all markers). Expression of all markers is significantly higher in papillary carcinoma than in follicular adenoma (p < 0.01). Statistically significant difference in expression of Galectin-3 and CD56 between follicular carcinoma and follicular adenoma was registered (p = 0.043; p = 0.028, respectively). The only marker which expression showed statistically significant difference between adenoma and carcinoma of Hurthle cells was Galectin 3 (p = 0.041). CK19 and HBME-1 were significantly expressed more in papillary carcinoma as compared to follicular carcinoma.

Conclusion: Galectin 3 is most sensitive marker for malignancy, while loss of expression of CD56 is very specific for malignancy. Expected co-expression for combination of markers in diagnosis of follicular lesions decreases sensitivity and increases specificity for malignancy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adenocarcinoma, Follicular* / diagnosis
  • Adenocarcinoma, Follicular* / metabolism
  • Adult
  • Aged
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / metabolism
  • CD56 Antigen* / metabolism
  • Carcinoma, Papillary / pathology
  • Female
  • Galectin 3* / metabolism
  • Humans
  • Keratin-19* / metabolism
  • Male
  • Middle Aged
  • Thyroid Neoplasms* / diagnosis
  • Thyroid Neoplasms* / metabolism


  • Biomarkers, Tumor
  • CD56 Antigen
  • Galectin 3
  • HBME-1 antigen
  • Keratin-19