Different expression of protein kinase A (PKA) regulatory subunits in normal and neoplastic thyroid tissues

Stefano Ferrero^1,2, Valentina Vaira², Alessandro del Gobbo², Leonardo Vicentini³, Silvano Bosari^4,2, Paolo Beck-Peccoz⁵, Giovanna Mantovani⁵, Anna Spada⁵ and Andrea G. Lania<sup>6

1</sup>Department of Biomedical, Surgical and Dental Sciences, University of Milan Medical School, ²Division of Pathology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, ³Endocrine Surgery Unit, Fondazione IRCCS Ca' Granda – Ospedale Maggiore Policlinico, ⁴Department of Pathophysiology and Organ Transplant, University of Milan Medical School, ⁵Endocrinology and Diabetology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and ⁶Endocrinology Unit, IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy

Offprint requests to: Stefano Ferrero MD, Department of Biomedical, Surgical and Dental Sciences, University of Milan Medical School, Milan, Italy- Fondazione IRCCS "Ca' Granda" - Ospedale Maggiore Policlinico, Vai F. Sforza 35. Milano, 20122, Italy. e-mail: stefano.ferrero@unimi.it

Summary. 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. Histol Histopathol 30, 473-478 (2015)

Key words: PKA, Thyroid neoplasia, PRKAR1A, PRKAR2B

DOI: 10.14670/HH-30.473