Mucosal high apoptotic activity and low p21WAF1/CIP1 expression and submucosal low proliferative activity in superficially spreading early gastric cancers: Comparison with the penetrating growth type

In order to investigate cell kinetics and cell cycle regulator protein expression with reference to the growth pattern of early gastric carcinomas (EGCs), we evaluated a total of 240 EGCs with submucosal invasion clinicopathologically and 106 submucosal invasive lesions immunohistochemically. The incidence of lymph node metastasis was relatively high (36.4%) in the superficially spreading growth (SUP) type tumors whereas the penetrating growth (PEN) type had a low incidence (5.7%, P < 0.001) and correlated with submucosal tumor size. Ki67 labeling was lower in submucosal areas of the SUP-type tumors (median, 37.3%) than the PEN-type tumors (51.0%, P < 0.001). ssDNA labeling in the lamina propria, indicative of apoptotic activity, was higher in the SUP-type tumors (0.55%) than in PEN-type (0.30%, P < 0.01) lesions. The expression of cell cycle regulator p21WAF1/CIP1 was lower in the SUP-type tumors (lamina propria 15.6%, submucosa 2.6%) than in PEN-type tumors (lamina propria 26.5%, submucosa 4.4%, P < 0.05-0.001). In conclusion, differences in cell kinetics and p21WAF1/CIP1 expression might influence the growth pattern of EGCs. The SUP-type EGC, characterized by high apoptotic in the lamina propria and low proliferative activities in the submucosa, is associated with frequent lymph node metastasis, suggesting a strong correlation between tumor size in the submucosa and metastatic potential.