Send to:

Choose Destination
See comment in PubMed Commons below
Am J Pathol. 2001 Mar;158(3):987-96.

Beta-catenin dysregulation in thyroid neoplasms: down-regulation, aberrant nuclear expression, and CTNNB1 exon 3 mutations are markers for aggressive tumor phenotypes and poor prognosis.

Author information

  • 1Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.


beta-catenin has a role in cell adhesion and Wnt signaling. It is mutated or otherwise dysregulated in a variety of human cancers. In this study we assess beta-catenin alteration in 145 thyroid tumors samples from 127 patients. beta-catenin was localized using immunofluorescence and mutational analysis was performed by single-strand conformational polymorphism. Membrane beta-catenin expression was decreased in eight of 12 (66%) adenomas and in all 115 carcinomas (P: < 0.0001). Among carcinomas, reduced membrane beta-catenin was associated with progressive loss of tumor differentiation (P: < 0.0001). CTNNB1 exon 3 mutations and nuclear beta-catenin localization were restricted to poorly differentiated [7 of 28 (25%) and 6 of 28 cases (21.4%), respectively] or undifferentiated carcinomas [19 of 29 (65.5%) and 14 of 29 (48.3%) cases, respectively]. Poorly differentiated tumors always featured mutations involving Ser and Thr residues and were characterized by Thr to Ile amino acid substitutions (P: = 0.0283). The association between CTNNB1 exon 3 mutations and aberrant nuclear immunoreactivity (P: = 0.0020) is consistent with Wnt activation because of stabilizing beta-catenin mutations. Low membrane beta-catenin expression as well as its nuclear localization or CTNNB1 exon 3 mutations are significantly associated with poor prognosis, independent of conventional prognostic indicators for thyroid cancer but not of tumor differentiation. Analysis of beta-catenin dysregulation may be useful to objectively subtype thyroid neoplasms and more accurately predict outcomes.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk