SUPPRESSED APOPTOTIC INDUCTION IN ESOPHAGEAL SQUAMOUS-CELL CARCINOMASEXPRESSING EXTENSIVE P53 PROTEIN

p53 protein accumulation, thought to be caused by p53 gene mutation, i s closely related to poor prognosis of patients with certain types of carcinomas. The progression of esophageal squamous cell carcinoma (SCC ) is also strongly suspected to depend on the p53 tumor suppressor gen e. Formalin-fixed, paraffin-embedded sections were taken from 25 patie nts who underwent esophagectomy for SCC. Fourteen patients had no preo perative therapy (control group), while the other 11 patients received preoperative radiotherapy (radiation group). There was no difference in pathological TNM classification between the two groups. These secti ons were examined by immunostaining with monoclonal antibody PAb 1801 to determine the accumulation of p53 protein,and apoptotic frequency w as determined by TdT mediated dUTP-biotin nick end-labeling (TUNEL). I n the control group, well to moderately differentiated cases showed a significantly higher AI (apoptotic index which is the number of apopto tic cells among 1000 cancer cells. parts per thousand) (51.7+/-83.4) t han poorly differentiated cases (AI=1.3+/-1.0) (P<0.05). Similar resul ts were obtained in the radiation group. The former group included 4 c ases of p53 grade 4 (p53 protein detected in over 70% of the tumor cel ls), and the latter included 2. Few apoptotic cells were observed in a ny of 6 tumor tissues. In each patient, tumor cells with accumulated p 53 protein were very rare to be apoptotic. On the other hand, apoptosi s was observed in tumor cells without p53 protein accumulation. Sponta neous apoptosis in esophageal SCC can be induced more easily in differ entiated than in poorly differentiated cases. This tendency may be enh anced by preoperative radiotherapy. Extensive p53 protein may suppress apoptotic induction in esophageal squamous cell carcinomas.