title: Vital staining with iodine solution in oral cancer: iodine infiltration, cell proliferation, and glucose transporter 1.
abstract: BACKGROUND
  Vital staining with iodine solution has been used to distinguish dysplastic/malignant oral epithelium from normal mucosa. However, little is known about its critical mechanism. The purpose of this study was to visualize how iodine infiltrates the oral epithelium and reacts with glycogen. In addition, we tested the hypothesis that higher cell proliferation requires increased energy consumption, and consequently exhausted glycogen may lead to a failure to be stained by iodine solution.
  
  
  METHODS
  Fifteen frozen tissue samples of iodine-stained and -unstained mucosa were obtained from 15 cases of oral squamous cell carcinoma (OSCC). Serial frozen sections were cut and examined with hematoxylin and eosin and periodic acid-Schiff methods and immunohistochemical staining for p53, Ki67 and glucose transporter 1 (GLUT 1).
  
  
  RESULTS
  Iodine solution was able to penetrate normal epithelium to a maximum depth neighboring the parabasal layer, but iodine-stained areas were completely consistent with glycogen distribution only in the upper superficial layer. Iodine-negative epithelium presented significantly higher immunoreactions for P53 and GLUT 1 in basal, parabasal, and superficial layers, respectively, whereas the reaction for Ki67 in the superficial layer was higher than that in iodine-positive epithelium (Wilcoxon signed-rank test, P < 0.05).
  
  
  CONCLUSIONS
  Iodine infiltrated and reacted with glycogen mainly in the upper superficial layer of the nonkeratinized epithelium. Both histological and molecular margins can be confirmed by iodine vital staining in OSCC. It is also suggested that high cell proliferation induced elevated glycolysis, resulting in an intraepithelial glycogen degradation and consequent failure to be stained by iodine solution.
authors: Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
authors: Tiepeng
authors: T
authors: Xiao
authors: Hiroshi
authors: H
authors: Kurita
authors: Tetsu
authors: T
authors: Shimane
authors: Yoshitaka
authors: Y
authors: Nakanishi
authors: Takeshi
authors: T
authors: Koike
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007455:Iodine / Q000737:chemistry / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D013194:Staining and Labeling; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; D019394:Ki-67 Antigen; C495677:SLC2A1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D006003:Glycogen; D007455:Iodine