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Updated: Jan 16, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Immunohistochemical analysis reveals increased active GSK3 and inactive PP2A levels in anaplastic thyroid cancer
Fereshteh Bahari1,2, Majid Mossahebi-Mohammadi2, Hilda Samimi2
1Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Objectives:
Anaplastic thyroid carcinoma (ATC) is a lethal subtype of thyroid cancer with a poor prognosis. Due to the lack of promising treatment opportunities for ATC, gaining a better understanding of the molecular mechanisms underlying tumorigenesis seems crucial. Here, we focused on two major players in the Wnt signaling pathway.
Methods:
The expression of PP2A and GSK3α/β proteins was studied in 12 ATC and 15 goiter formalin-fixed paraffin-embedded tissue samples using immunohistochemistry. The intensity of nuclear staining in tumor cells, as well as the total scores of protein expression, were calculated.
Results:
The expression of inactive PP2A and active GSK3α/β proteins was negative in all control (goiter) samples. Both proteins were expressed in all ATC samples at different levels. Notably, eight samples represented strong expression (percentage = 100; total score = 300) of both proteins. The average total score staining was 210.3 for the phosphorylated and active form of GSK3α/β (Y279/216) and 274.5 for phosphorylated PP2A at Y307 and its inactive form. For features such as age, gender, greatest diameter of tumors, as well as PP2A and GSK3α/β total staining scores, no significant differences were observed between metastatic and nonmetastatic cases. Similarly, no association was demonstrated between metastasis with demographic and tumor characteristics.
Conclusions:
The current study investigated the expression of PP2A and GSK3α/β, two key proteins in the Wnt signaling pathway, in ATC tissue samples. Although this study highlights the importance of PP2A and GSK3α/β in ATC, a clear understanding of PP2A and GSK3α/β dysregulation and function in ATC remains to be elucidated.
Insights
Anaplastic thyroid carcinoma (ATC) involves Wnt signaling proteins PP2A and GSK3α/β. These proteins are expressed in ATC but not in goiter tissue, though their role in metastasis requires further study.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Anaplastic thyroid carcinoma (ATC) is an aggressive cancer with limited treatment options.
- Understanding the molecular drivers of ATC tumorigenesis is critical for developing new therapies.
- The Wnt signaling pathway plays a significant role in various cancers, including thyroid cancer.
Purpose of the Study:
- To investigate the expression of protein phosphatase 2 (PP2A) and glycogen synthase kinase 3 alpha/beta (GSK3α/β) in anaplastic thyroid carcinoma.
- To determine the potential role of PP2A and GSK3α/β in the context of ATC tumorigenesis and metastasis.
Main Methods:
- Immunohistochemistry was employed to analyze PP2A and GSK3α/β protein expression in 12 ATC and 15 goiter tissue samples.
- Quantitative analysis of nuclear staining intensity and total protein expression scores was performed.
Main Results:
- PP2A and GSK3α/β were expressed in all ATC samples, with varying levels, but were absent in control (goiter) samples.
- Strong expression of both proteins was observed in eight ATC samples.
- No significant differences in protein expression were found between metastatic and non-metastatic ATC cases, nor were associations found between metastasis and demographic/tumor characteristics.
Conclusions:
- PP2A and GSK3α/β are expressed in anaplastic thyroid carcinoma tissue.
- While highlighting the importance of these proteins in ATC, their precise dysregulation and function in the disease remain to be fully elucidated.
