Correlation of histologic morphology and tumor stage with molecular genetic analysis using microdissection in gastric carcinomas

Precise correlation of histomorphology with the results of molecular geneti c analysis is difficult in gastric cancer tissue composed of intestinal and diffuse types. A novel microdissection procedure was applied to correlate p53 and APC allelic loss with histologic type and tumor stage (mucosal vs. invasive cancer) in formalin-fixed, paraffin-embedded specimens of 25 gastr ic cancers. In addition, mucosal and invasive lesions were dissected from e ach of 11 invasive gastric cancers to study progression, and allelic loss o f the p53 and APC genes was assessed. The p53 gene underwent loss of hetero zygosity (LOH) in 4 of 4 informative cases of intestinal-type gastric cance r with mucosal lesions associated with invasion. By contrast, no p53 LOH wa s found among 6 informative cases with mucosal cancer. LOH of the APC gene in both intestinal and diffuse types of cancer was detected in 4 of 7 and 5 of 6 informative cases, respectively. These data suggest that allelic dele tion of the p53 gene in intestinal-type gastric carcinoma predicts the inva sive potential of mucosal cancer, and that inactivation of the APC gene pla ys a role in the genetic tumorigenesis of both intestinal and diffuse types of gastric cancer. Microdissection can correlate genetic alterations with histologic morphology in gastric cancer.