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Updated: Apr 21, 2026

An Ex vivo Culture System to Study Thyroid Development
Published on: June 6, 2014
Different expression of protein kinase A (PKA) regulatory subunits in normal and neoplastic thyroid tissues
Stefano Ferrero1, Valentina Vaira2, Alessandro Del Gobbo2
1Department of Biomedical, Surgical and Dental Sciences, University of Milan Medical School, and Division of Pathology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy. stefano.ferrero@unimi.it.
Abstract:
The four regulatory subunits (R1A, R1B, R2A, R2B) of protein kinase A (PKA) are differentially expressed in several cancer cell lines and exert distinct roles in both cell growth and cell differentiation control. Mutations of the PRKAR1A gene have been found in patients with Carney complex and in a minority of sporadic anaplastic thyroid carcinomas. The aim of the study was to retrospectively evaluate the expression of different PKA regulatory subunits in benign and non benign human thyroid tumours and to correlate their expression with clinical phenotype. Immunohistochemistry demonstrated a significant increase in PRKAR2B expression in both differentiated and undifferentiated (anaplastic) thyroid tumors in comparison with normal thyroid tissues. Conversely, a significant increase in PRKAR1A expression was only demonstrated in undifferentiated thyroid carcinomas in comparison with normal thyroid tissue and differentiated thyroid tumors. In thyroid cancers without lymph nodal metastases PRKAR1A expression was higher in tumours of more than 2 cm in size (T2 and T3) compared to smaller ones (T1). In conclusion, our data shows that an increased PRKAR1A expression is associated with aggressive and undifferentiated thyroid tumors.
Insights
Increased expression of protein kinase A (PKA) regulatory subunit A (PRKAR1A) is linked to aggressive, undifferentiated thyroid tumors. PRKAR2B also increased in thyroid tumors compared to normal tissue.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Protein kinase A (PKA) regulatory subunits (R1A, R1B, R2A, R2B) have distinct roles in cell growth and differentiation.
- PRKAR1A gene mutations are implicated in Carney complex and some anaplastic thyroid carcinomas.
Purpose of the Study:
- To examine PKA regulatory subunit expression in benign and malignant thyroid tumors.
- To correlate subunit expression with clinical and pathological features of thyroid tumors.
Main Methods:
- Retrospective analysis of thyroid tumor tissues.
- Immunohistochemistry to detect PRKAR1A, PRKAR1B, PRKAR2A, and PRKAR2B expression.
- Correlation of expression levels with tumor type, grade, size, and lymph node metastasis.
Main Results:
- PRKAR2B expression was elevated in both differentiated and undifferentiated thyroid tumors versus normal thyroid tissue.
- PRKAR1A expression was significantly increased in undifferentiated (anaplastic) thyroid carcinomas compared to normal and differentiated tumors.
- Higher PRKAR1A expression correlated with larger tumor size (T2/T3 vs. T1) in non-metastatic thyroid cancers.
Conclusions:
- Elevated PRKAR1A expression is associated with aggressive, undifferentiated thyroid tumors.
- PRKAR2B upregulation occurs broadly in thyroid tumorigenesis.
- PRKAR1A may serve as a marker for aggressive thyroid cancer phenotypes.
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