Cell proliferation and differentiation in intramucosal and advanced signet ring cell carcinomas of the human stomach

In order to study the progression of signet ring cell carcinomas in the human stomach, we compared cell proliferation and differentiation between small and large intramucosal cancers, and between intramucosal and advanced cancers. Fine-structurally, signet ring cells were differentiated to 3 cell types: a foveolar, a glandular and an intestinal type. In the mucosa, the foveolar-type cells and glandular-type cells were distributed at the superficial and the deep zone, respectively. In the small mucosal cancers, intestinal-type cells were rare and a layered structure was often seen. In this structure, the mode of cell production resembled that in the normal gastric mucosa; the foveolar-type signet ring cells in the superficial layer were not proliferative and the proliferating cells were small cells in the middle layer and a few glandular-type cells in the deep layer. In the large mucosal and advanced cancers, intestinal-type cells and proliferating small round cells were often distributed throughout the depth of the mucosa, and signet ring cells of the foveolar type were also proliferative. These findings indicated that large part of the signet ring cell carcinomas initially form the layered structure and that it becomes indistinct while intestinal-type cells appear as the tumour grows. However, we found several small advanced cancers, lacking both the layered structure and the intestinal-type cells. These cancers appear to start without the layered structure and progress very rapidly.