Association of nuclear, cytoplasmic expression of galectin-3 with beta-catenin/Wnt-pathway activation in thyroid carcinoma

Arch Otolaryngol Head Neck Surg. 2007 May;133(5):503-10. doi: 10.1001/archotol.133.5.503.

Abstract

Objectives: To characterize the localization of galectin-3 in benign and malignant thyroid neoplasms and to correlate this with alterations in beta-catenin and cyclin D1 expression.

Design: Immunohistochemical study of 116 paraffin-embedded archival specimens from 113 patients who had undergone thyroidectomy and tissue placed into a commercially available tissue microarray.

Setting: Tertiary care hospital.

Interventions: Thyroid tissue microarrays were stained by standard immunohistochemical protocols with monoclonal antibodies against galectin-3, beta-catenin, and cyclin D1.

Main outcome measures: Nuclear and cytoplasmic expression of galectin-3 was correlated with clinical parameters, beta-catenin, and cyclin D1 expression.

Results: Both cytoplasmic (56%) and nuclear (42%) galectin-3 expression was observed in most malignant neoplasms but was absent in benign thyroid specimens (P<.001). Among carcinomas, cytoplasmic galectin-3 expression was observed in papillary thyroid carcinomas (82%) and follicular (33%) and medullary (9%) carcinomas but was absent in anaplastic carcinomas (P<.001). Galectin-3 nuclear expression was observed in papillary thyroid carcinomas (62%) and follicular carcinomas (33%) but was undetectable in medullary, anaplastic carcinomas (P<.001). Cytoplasmic but not nuclear galectin-3 was inversely correlated with American Joint Committee on Cancer TNM stage (P = .02). There was a strong correlation between cytoplasmic and nuclear beta-catenin expression and both nuclear (P = .04) and cytoplasmic (P = .003) galectin-3 expression. Similarly, there was a strong association between galectin-3 nuclear (P<.001) and cytoplasmic (P<.001) expression and cyclin D1 expression.

Conclusion: Cytoplasmic and nuclear galectin-3 expression seem to be associated with activation of the Wnt-signaling pathway in well-differentiated thyroid neoplasms, suggesting that galectin-3 plays a role in thyroid carcinogenesis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Proteins / genetics*
  • Blood Proteins / metabolism
  • Female
  • Galectin 3 / genetics*
  • Galectin 3 / metabolism
  • Gene Expression Regulation / genetics*
  • Genes, bcl-1 / genetics
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Protein Array Analysis / methods
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Sensitivity and Specificity
  • Signal Transduction / genetics*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology
  • Wnt Proteins / genetics*
  • Wnt Proteins / metabolism
  • beta Catenin / genetics*
  • beta Catenin / metabolism

Substances

  • Blood Proteins
  • Galectin 3
  • Receptors, Cytoplasmic and Nuclear
  • Wnt Proteins
  • beta Catenin
  • cytoplasmic activator protein, human