This suggested that the therapeutic strategy of ESCC may be more complicated than other malignancies: the combination of immunotherapeutic strategies and molecular target therapy may be possibly applicable and the PD-L1 expression in PD-L1-postive ESCCs and PIK3CA mutation in PD-L1-negative ESCCs may be beneficial in curatively resected ESCCs. This evidence concerns the gene PIK3CA and esophageal squamous cell carcinoma.