Imunolocalização das proteínas Shh, Gli-1 e Fgf-2 em adenomas de células basais de glândulas salivares

Abstract

The basal cell adenoma (BCA) is a rare benign tumor of the salivary glands that primarily affects the parotid salivary gland. The causes and mechanisms involved in its pathogenesis are poorly understood. Researches have shown nuclear accumulation of β-Catenin in BCA. β-Catenin is related to the Wnt signaling pathway, but recent studies were not able to show activation of this pathway in BCA, suggesting that the its nuclear accumulation is not related to the presence of the Wnt pathway. The Hedgeghog (HH) signaling pathway has many interfaces with Wnt pathway, including ability to translocate β-Catenin to the nucleus and therefore activate cellular proliferation and it is known that excessive HH signaling pathway can lead to cancer and metastasis, but immunohistochemistry detection of proteins in this pathway was not yet studied in BCA. The aim of this study was to investigate the presence of proteins related to HH pathway in BCA, to improve the knowledge, the pathogenesis about this lesion and if it could relate to the nuclear accumulation of β-catenin. In 21 cases of BCA, by immunohistochemistry using streptavidin-biotin-peroxidase technique, we studied the proteins Shh, the main activator of the HH pathway, Gli-1, which is related to HH signal transduction, and also Fgf-2, an important inhibitor of cell proliferation induced by Shh in neuronal precursors and tumor cells, but in normal skin Fgf-2 showed an inductor role of Shh and β-catenin. Each reaction was analyzed qualitatively and quantitatively by QuickScore Index (QI). We found weak cytoplasmic reactivity in 71.4% of the cases to Shh, and 52.4% to Gli-1. Fgf-2 was observed varied cytoplasmic and nuclear staining in 100% of the cases. For all antigens, staining was similar in both luminal and abluminal cells. The average QI were 1.7, 1.6 and 8.5 to Shh, Gli-1 and Fgf-2, respectively. There was a positive correlation only between Shh and Fgf-2. Suggesting the existence of a positive feedback in which Fgf-2 has an inhibitory effect over Shh, showing a similar action to that found in neuronal precursors and tumor cells. These results do not confirm activation of the HH pathway in BCA, and is not related with the nuclear accumulation of β-catenin. But suggest that Fgf-2 has a tumor inducing action and also could represent the explanation of typical β-catenin found in this lesion.