Abstract
BackgroundThe sodium/iodide symporter (NIS) is a plasma membrane glycoprotein that mediates iodide (I-) transport in the thyroid, lactating breast, salivary glands, and stomach. Whereas NIS expression and regulation have been extensively investigated in healthy and neoplastic thyroid and breast tissues, little is known about NIS expression and function along the healthy and diseased gastrointestinal tract.MethodsThus, we investigated NIS expression by immunohistochemical analysis in 155 gastrointestinal tissue samples and by immunoblot analysis in 17 gastric tumors from 83 patients.ResultsRegarding the healthy Gl tract, we observed NIS expression exclusively in the basolateral region of the gastric mucin-producing epithelial cells. In gastritis, positive NIS staining was observed in these cells both in the presence and absence of Helicobacter pylori. Significantly, NIS expression was absent in gastric cancer, independently of its histological type. Only focal faint NIS expression was detected in the direct vicinity of gastric tumors, i.e., in the histologically intact mucosa, the expression becoming gradually stronger and linear farther away from the tumor. Barrett mucosa with junctional and fundic-type columnar metaplasia displayed positive NIS staining, whereas Barrett mucosa with intestinal metaplasia was negative. NIS staining was also absent in intestinalized gastric polyps.ConclusionThat NIS expression is markedly decreased or absent in case of intestinalization or malignant transformation of the gastric mucosa suggests that NIS may prove to be a significant tumor marker in the diagnosis and prognosis of gastric malignancies and also precancerous lesions such as Barrett mucosa, thus extending the medical significance of NIS beyond thyroid disease.
Highlights
The sodium/iodide symporter (NIS) is a plasma membrane glycoprotein that mediates iodide (I-) transport in the thyroid, lactating breast, salivary glands, and stomach
NIS-mediated active I- uptake has long been viewed as a distinctly thyroidal phenomenon, it is clear that active I- transport observed in extrathyroidal tissues such as salivary glands, lactating mammary gland, gastric mucosa, and placenta is mediated by NIS [38]
Immunohistochemical analysis of NIS in the thyroid, salivary glands, and stomach revealed very distinctly in which particular cells NIS is located in each tissue, namely the thyroid epithelial (Fig. 1C,D), salivary gland ductal epithelial (Fig. 1E,F), and gastric mucin-producing epithelial cells (Fig. 1G,H)
Summary
The sodium/iodide symporter (NIS) is a plasma membrane glycoprotein that mediates iodide (I-) transport in the thyroid, lactating breast, salivary glands, and stomach. Iodide (I-) is an essential constituent of the thyroid hormones triiodothyronine (T3) and tetraiodothyronine (T4) These hormones are vital for the normal development and maturation of the central nervous system in the newborn and for multiple metabolic functions in the adult. A cornerstone of I- metabolism is active I- uptake in the thyroid, a process mediated by the sodium/iodide symporter (NIS)[1,2]. NIS-mediated active I- uptake has long been viewed as a distinctly thyroidal phenomenon, it is clear that active I- transport observed in extrathyroidal tissues such as salivary glands, lactating mammary gland, gastric mucosa, and placenta is mediated by NIS [38]. NIS-mediated radioiodide uptake in the stomach and salivary glands is routinely observed in radioiodide/99mTcO4 -whole-body scintiscans (Fig 1A) [9]
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