P53 expression and p21 expression are mutually exclusive in esophageal squamous cell carcinoma

The accumulation of p53 protein, which is considered to be caused by a p53 gene mutation, is closely associated with poor prognosis in patients with certain types of carcinomas. The progression of esophageal squamous cell carcinoma (ESCC) is also suspected to depend on p53 gene status. We analyzed the relationship between p53 and p21 protein accumulation in ESCC, and simultaneously analyzed the frequency of apoptosis. Formalin-fixed paraffin-embedded sections were taken from 46 patients who underwent esophagectomy for ESCC. These sections were examined by immunostaining with monoclonal antibodies PAb1801 and EA10 to determine p53 and p21 protein accumulation, respectively. We also analyzed the frequency of apoptosis by TdT-mediated dUTP-biotin nick end-labeling (TUNEL). For estimation of the proportion of stained cells, we used computer analysis with NIH image analysis software. p21 protein accumulation showed an almost inverse distribution to that of p53 protein. In areas where both p53 and p21 proteins were accumulated, few apoptotic cells were observed. Particularly in cases of mucosal tumors, p53 protein was prominently accumulated in the lower layer of the tumor, whereas p21 protein accumulation was confined to the upper layer. Our results suggest that progression of esophageal squamous cell carcinoma is controlled by a p53-dependent pathway.