Claudin-1 and -7 Expression in Solid Cell Nests of the Thyroid: An Enigmatic Analogy with Papillary Carcinoma.
Chiara Colato, Alessandra Fierabracci, Angela Dardano, Fabio Monzani, Marco Chilosi, Guido Martignoni, Fabio Menestrina, Marco Ferdeghini. University of Verona, Italy; Children's Hospital Bambino Gesù, IRCCS, Rome, Italy; University of Pisa, Italy
Background: Solid cell nests (SCNs), a normal component of the human thyroid gland, are considered remnants of the ultimobranchial body. The immunohistochemical profile of SCNs is well characterized and, as they apparently harbor the minimal properties of a stem cell phenotype, can be regarded as a pool of stem cells of the adult thyroid. Moreover, both the immunohistochemical detection of p63 in SCNs and BRAF mutation in solid cell nest hyperplasia suggest a link between these embryonic remnants and papillary thyroid carcinoma (PTC). However the biological significance of SCNs remains disputable. Claudins (CLDNs), a family of tight junction proteins, play a role in adhesion, cell proliferation, and tumorigenesis. Recently, CLDN1 was found to be up-regulated in PTC both at the gene and protein level. CLDN7 is also expressed in the thyroid, both during embryonic development and in the adult, and its expression is modulated in thyroid cancer.
Design: To assess the immunohistochemical expression of CLDN1 and 7 in a collection of 20 SCNs, found incidentally in specimens resected for PTC, follicular adenomas and multinodular goiter as well as to compare their staining pattern with that of PTC.
Results: In all cases, SCNs displayed a strong, diffuse and linear membranous CLDN1 positivity, forming a honeycomb-like pattern. In contrast, the C cells were constantly negative and in normal thyroid tissue only scattered positive cells were observed. CLDN7 staining was similar to that of CLDN1 with strong or moderate intensity.
Conclusions: We report for the first time CLDN1 and 7 expression in SCNs. CLDN1 appears a highly sensitive tool in detecting SCNs, as described for p63 and Galectin-3. CLDN7 is constantly expressed in SCNs as in fetal and adult thyroid, suggesting a potential role in architectural stability and functioning of follicular cells. We confirm that CLDN1 is frequently up-regulated in PTC and may represent a novel marker for this tumor as well as Galectin-3. This finding suggests the hypothesis of a histogenetic link between SCNs and PTC. Finally, CLDN1 may also be useful in separating SCNs from C cells, as normal C cells do not express this membrane protein.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 35, Tuesday Afternoon