Vital staining with iodine solution in oral cancer: iodine infiltration, cell proliferation, and glucose transporter 1

• Published in: International journal of clinical oncology Vol. 18; no. 5; pp. 792 - 800
• Main Authors: Xiao, Tiepeng, Kurita, Hiroshi, Shimane, Tetsu, Nakanishi, Yoshitaka, Koike, Takeshi
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.10.2013; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Cancer Research; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell adhesion & migration; Cell Proliferation; Epithelium - metabolism; Epithelium - pathology; Female; Gene Expression Regulation, Neoplastic; Glucose; Glucose Transporter Type 1 - metabolism; Glycogen - metabolism; Humans; Iodine - chemistry; Iodine - metabolism; Ki-67 Antigen - metabolism; Male; Medicine; Medicine & Public Health; Middle Aged; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Mouth Neoplasms - surgery; Oncology; Original Article; Salt; Staining and Labeling; Surgery; Surgical Oncology; Tissues; Tumor Suppressor Protein p53 - metabolism; Oral squamous cell carcinoma; Mucosal surgical margin; GLUT 1; Glycogen; Iodine vital staining
• ISSN: 1341-9625; 1437-7772
• DOI: 10.1007/s10147-012-0450-4

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.