Claudin Proteins, PAX8 and NIS Immunohistochemical Evaluation in Human Fetal Thyroid Development
C Colato, MC Ambrosetti, A Dardano, F Monzani, S Filetti, M Chilosi, F Menestrina, M Ferdeghini. University of Verona, Verona, Italy; University of Pisa, Pisa, Italy; University La Sapienza, Roma, Italy
Background: thyroid gland derives from aggregates of unpolarized cells. Pax8, a family of developmental control genes that encode transcription factors, is crucial for thyroid organogenesis and differentiation. The Na+/I- symporter (NIS) is a critical gene involved in the active I- accumulation into the thyroid gland, the first step in thyroid hormone synthesis. Tight junctions (TJs) are dynamic structures, that at different stages of epithelial tissue development play a role in maintaining integrity and physiological function of polarized epithelial cells. Claudins (CLDNs) form the backbone of TJs. They expression during thyroid ontogenesis is unknown.
Design: we analyzed the immunohistochemical expression of CLDNs-1,3,4,5,7, Pax8 and NIS in 19 human fetal thyroid glands (15-27 gestational weeks; from elective/voluntary abortions or autopsies).
Results: CLDN7 was constantly expressed showing strong, diffuse and linear basolateral positivity. CLDN5 and 4 staining appeared as a thin line or dot-like along the lateral membrane with discontinuous pattern. CLDN1 exhibited strong, linear or dot membranous staining on the gland periphery. CLDN3 immunoreactivity was negative. Pax8 was observed in a nuclear pattern in all samples. NIS displayed strong basolateral staining in most of the follicular cells.
Conclusions: CLDN7 is consistently expressed in thyroid epithelium during ontogenesis at a similar level from fetal to adult thyroid tissue, thus suggesting a pivotal role in architectural stability of follicular cells. CLDN1 was noted only at the border of the fetal gland: the exact role for this membrane protein is still not clear. Conversely, CLDN1 was weakly expressed in adult normal tissue while was up-regulated in thyroid cancer, thus emerging as an oncofetal antigen and a potential marker of thyroid cancer. CLDN4 exhibited high expression in thyroid fetal gland while was down-regulated in adult thyroid tissue, suggesting a physiological involvement in the development and functioning of thyroid follicles. Our study demonstrates, for the first time, that CLDN5 was expressed both in fetal and adult thyroid tissue showing a similar distribution and staining pattern. Finally, we confirm that Pax8 and NIS are expressed at an early stage of ontogenesis playing a key role in thyroid development and differentiation.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 44, Tuesday Afternoon