Expression of the Na+/I- symporter (NIS) is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus.
BACKGROUND
The 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.


METHODS
Thus, we investigated NIS expression by immunohistochemical analysis in 155 gastrointestinal tissue samples and by immunoblot analysis in 17 gastric tumors from 83 patients.


RESULTS
Regarding 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.


CONCLUSIONS
That 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.
Altorjay
Aron
A
Department of Surgery, St. George University Teaching Hospital H-8000 Székesfehérvár, Hungary. altorjay@mail.fmkorhaz.hu <altorjay@mail.fmkorhaz.hu>
Dohán
Orsolya
O
Szilágyi
Anna
A
Paroder
Monika
M
Wapnir
Irene L
IL
Carrasco
Nancy
N
D001471:Barrett Esophagus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007455:Iodine / Q000378:metabolism; D008297:Male; D008679:Metaplasia / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D027981:Symporters / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D000099209:Sodium-Iodide Symporters
D014408:Biomarkers, Tumor; D007455:Iodine; D027981:Symporters; D000099209:Sodium-Iodide Symporters