SOX2 is highly expressed in squamous cell carcinomas of the gastrointestinal tract.

SOX2 is a high-mobility group box embryonic stem cell transcription factor that is expressed in the developing foregut and normal gastric epithelium and is downregulated in intestinal metaplasia of the stomach and esophagus. In addition, SOX2 colocalizes with p63 in the basal layer and plays a critical role in the maintenance of the stratified squamous epithelium of the esophagus. SOX2 expression in squamous cell carcinomas of the gastrointestinal tract has not been previously evaluated. The purpose of this study was to determine whether SOX2 is differentially expressed in squamous cell carcinomas versus adenocarcinomas of the esophagus and rectum/anal canal and to compare its expression to p63, cytokeratin 5/6, and CDX2. In total, 93 tumors were evaluated: 26 esophageal squamous cell carcinomas, 23 esophageal adenocarcinomas, 21 squamous cell carcinomas of the anal canal, and 23 rectal adenocarcinomas. SOX2 was expressed in 81% of esophageal squamous cell carcinomas and 91% of anal canal squamous cell carcinomas, compared to 13% and 17% of esophageal and rectal adenocarcinomas, respectively. p63 was expressed in 96% of esophageal squamous cell carcinomas and 100% of anal canal squamous cell carcinomas; the single squamous cell carcinoma negative for p63 was strongly positive for SOX2. Cytokeratin 5/6 was expressed in most esophageal and anal canal squamous cell carcinomas, but was also positive in 43% of esophageal adenocarcinomas and 13% of rectal adenocarcinomas. In summary, SOX2 is preferentially expressed in squamous cell carcinomas of the esophagus and anal canal compared to adenocarcinomas from these sites. SOX2 may be useful in an immunohistochemical panel to differentiate between squamous cell carcinomas and adenocarcinomas of the gastrointestinal tract.