FREQUENT OCCURRENCE OF APOPTOSIS IS AN EARLY EVENT IN THE ONCOGENESISOF HUMAN GASTRIC-CARCINOMA

We examined the relationship between apoptosis and the progression of human gastric carcinoma. Studies were conducted on a total of 88 surgi cally removed stomachs, comprising 26 minute (less than 5 mm in diamet er), 29 early (limited to the mucosal and submucosal layer) and 33 adv anced carcinomas. Apoptotic cells were visualized by terminal deoxynuc leotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labellin g (TUNEL). Serial sections were immunostained for p53 and Ki-67. The m ean apoptotic indices (AI: percentage of TUNEL signal positive cells) of minute, early, and advanced carcinomas were 4.1+/-0.6, 3.8+/-1.2, a nd 4.0+/-1.2 in 46 well differentiated carcinomas, and 2.1+/-0.5, 2.7/-0.9, and 2.2+/-1.1 in 42 poorly differentiated carcinomas, respectiv ely. Similarly, the mean Ki-67 labelling indices (KI) were 39.2+/-7.8, 47.2+/-12.8, 52.6+/-13.1 in the former, and 35.0+/-9.3, 36.9+/-10.3, and 40.0+/-9.2 in the latter, respectively. Both mean AI and mean KI w ere significantly higher in well differentiated than in poorly differe ntiated carcinomas (P<0.05). However, the value of mean AI did not dif fer among minute, early, and advanced carcinomas in either histologica l type, while KI increased gradually with tumour progression. The freq uency of nuclear p53 expression did not differ among the three categor ies, implying that the gene mutation is an early event in gastric carc inogenesis. There was no statistical significance between nuclear p53 expression and mean AI. These results suggest that the progression of gastric cancer is defined by a gradual increase of proliferative activ ity and constant occurrence of apoptosis and that naturally occurring apoptosis is induced predominantly via a p53-gene-independent pathway.