Progression of signet ring cell carcinomas in the human stomach

Background. Stomach cancers show various growth patterns. It remains to be clarified how this variability is related to the genetic changes that occur during tumor progression. Methods. To estimate the genetic changes from tumor ploidy, maps were made (using DNA cytofluorometry of metaphase cells in histologic sections) of 39 advanced signet ring cell carcinomas of the human stomach and correlated with tumor stage and the size of the primary mucosal lesion. Results. Aneuploid area and multipattern aneuploidy were particularly common in advanced cancers with primary mucosal lesions smaller than 2 cm in diameter, of which a large portion were predominantly aneuploid and already diffusely infiltrating. As the tumor stage advanced, the incidence of aneuploidy in the mucosal lesion increased, whereas predominantly aneuploid tumors were less common as primary mucosal lesions became larger. Purely diploid areas with an incidence of polyploidy as low as in early cancers were common in advanced cancers. In addition, there were diploid-appearing cancer cells that infiltrated diffusely and were accompanied by polyploid as often as aneuploid cells. Some of these were aneuploid at the chromosomal level. Conclusions. In signet ring cell carcinoma, aneuploid cells show higher invasive activity toward the extramucosal part and may occur incidentally in originally diploid tumors, depending on the degree of genetic instability. An analysis of polyploidy is useful for differentiating cytometrically diploid (but actually, aneuploid) cells from diploid cells with minor genetic abnormalities. Cancer 1993; 71:1938-47.