title: Modulation of sodium/iodide symporter expression in the salivary gland.
abstract: BACKGROUND
  Physiologic iodide-uptake, mediated by the sodium/iodide symporter (NIS), in the salivary gland confers its susceptibility to radioactive iodine-induced damage following (131)I treatment of thyroid cancer. Subsequent quality of life for thyroid cancer survivors can be decreased due to recurrent sialoadenitis and persistent xerostomia. NIS expression at the three principal salivary duct components in various pathological conditions was examined to better our understanding of NIS modulation in the salivary gland.
  
  
  METHODS
  NIS expression was evaluated by immunohistochemistry in human salivary gland tissue microarrays constructed of normal, inflamed, and neoplastic salivary tissue cores. Cumulative (123)I radioactivity reflecting the combination of NIS activity with clearance of saliva secretion in submandibular and parotid salivary glands was evaluated by single-photon emission computed tomography/computed tomography imaging 24 hours after (123)I administration in 50 thyroid cancer patients.
  
  
  RESULTS
  NIS is highly expressed in the basolateral membranes of the majority of striated ducts, yet weakly expressed in few intercalated and excretory duct cells. The ratio of (123)I accumulation between parotid and submandibular glands is 2.38±0.19. However, the corresponding ratio of (123)I accumulation normalized by volume of interest is 1.19±0.06. The percentage of NIS-positive striated duct cells in submandibular salivary glands was statistically greater than in parotid salivary glands, suggesting a higher clearance rate of saliva secretion in submandibular salivary glands. NIS expression in striated ducts was heterogeneously decreased or absent in sialoadenitis. Most ductal salivary gland tumors did not express NIS. However, Warthin's tumors of striated duct origin exhibited consistent and intense NIS staining, corresponding with radioactive iodine uptake.
  
  
  CONCLUSIONS
  NIS expression is tightly modulated during the transition of intercalated to striated ducts and striated to excretory ducts in salivary ductal cells. NIS expression in salivary glands is decreased during inflammation and tumor formation. Further investigation may identify molecular targets and/or pharmacologic agents that allow selective inhibition of NIS expression/activity in salivary glands during radioactive iodine treatment.
authors: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
authors: Krista M D
authors: KM
authors: La Perle
authors: Dong Chul
authors: DC
authors: Kim
authors: Nathan C
authors: NC
authors: Hall
authors: Adam
authors: A
authors: Bobbey
authors: Daniel H
authors: DH
authors: Shen
authors: Rebecca S
authors: RS
authors: Nagy
authors: Paul E
authors: PE
authors: Wakely
authors: Amy
authors: A
authors: Lehman
authors: David
authors: D
authors: Jarjoura
authors: Sissy M
authors: SM
authors: Jhiang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D010306:Parotid Gland / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism*; D012793:Sialadenitis / Q000378:metabolism; D013363:Submandibular Gland / Q000378:metabolism; D027981:Symporters / Q000096:biosynthesis*; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters