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β-Catenin expression in thyroid follicular lesions: Potential role in nuclear envelope changes in papillary carcinomas

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Abstract

The morphologic distinction of benign and malignant thyroid follicular lesions can sometimes be challenging, therefore an immunohistochemical marker to aid in this distinction would be useful. β-Catenin is one such potential marker. It is part of a membrane-bound cell growth-signaling complex that plays a role in cell adhesion, as well as in promotion of growth through activation of the Wnt signaling pathway. Oncogenic signaling occurs when β-catenin is released, accumulates in the cytoplasm, translocates into the nucleus, and promotes transcription of genes including bcl-1 (cyclin D1) and c-myc that induce cell proliferation.

Paraffin blocks from 133 thyroidectomy specimens were stained with monoclonal antibodies reactive with β-catenin and cyclin D1. These included 53 cases of papillary thyroid carcinoma (PTC), 46 cases of follicular variant of papillary carcinoma (FVPC), 10 cases of follicular carcinoma (FC), and 24 cases of follicular adenoma (FA). Tissue from six normal thyroid specimens served as a control. The malignant lesions (PTC, FC, and FVPC) expressed strong cytoplasmic/nuclear staining and minimal residual membranous staining in 87%, 80%, and 71% of cases, respectively. In contrast, all normal thyroid tissue and 79% of FAs showed strong membranous reactivity with very minimal cytoplasmic staining. Interestingly, in 83% of PTC cases and 20% FVPCs, the intranuclear inclusions were distinctly β-catenin positive. Cyclin D1 over expression correlated with cytoplasmic relocalization of β-catenin in almost all cases, and no evidence of cyclin D1 gene amplification was observed.

β-Catenin can be of a diagnostic utility for thyroid lesions, because it highlights intranuclear inclusions in PTC, and shifts from a membranous localization to a cytoplasmic localization in malignant lesions. We speculate that the localization of β-catenin in intranuclear inclusions may reflect a cytoskeletal remodeling activity of β-catenin that is functionally significant for the PTC pathway.

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Authors and Affiliations

  1. Department of Surgery, University of Massachusetts Medical School, Worcester, MA

    N. Patwardhan MD

  2. Department of Pathology, LAC+USC Medical Center, Los Angeles, CA

    R. K. Brynes MD, V. Nelson MD & M. Thein MD

  3. Department of Pathology, University of Massachusetts Medical School, University Campus, 55 Lake Avenue North, 01655, Worcester, MA, USA

    S. Rezk MD, A. Fischer MD &  A. Khan MD, FRCPath (Associate Professor of Pathology)

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  1. S. Rezk MD
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  2. R. K. Brynes MD
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  3. V. Nelson MD
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  4. M. Thein MD
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  5. N. Patwardhan MD
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  6. A. Fischer MD
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  7. A. Khan MD, FRCPath
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Correspondence to A. Khan MD, FRCPath.

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Rezk, S., Brynes, R.K., Nelson, V. et al. β-Catenin expression in thyroid follicular lesions: Potential role in nuclear envelope changes in papillary carcinomas. Endocr Pathol 15, 329–337 (2004). https://doi.org/10.1385/EP:15:4:329

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