Inactivation of this pathway was usually caused by mutations in key genes, such as gain-of-function mutations in PIK3CA and AKT, and loss of function mutations of PTEN. The detection of loss of function mutations in PTEN and gain of function mutations in PIK3CA in our study indicated different mechanisms of dysregulation of the PIK3CA/AKT pathway contributing to ESCC development. The gene discussed is PIK3CA; the disease is esophageal squamous cell carcinoma.