Molecular identification of main cellular lineages as a tool for the classification of gastric cancer

Gastric carcinomas (GC) are heterogeneous tumors comprising variable amount s of cells of different lineage phenotype, including gastric mucous cells ( surface-SMC or gland-GMC) and intestinal cells (IC). The evaluation of tumo r behavior has classically depended on strictly morphological classificatio ns of tumors. Microsatellite instability (MSI) is frequently detected in GC , but whether MSI affects all gastric cellular lineages or exclusively occu rs in unique cellular lineages in GC is not known. The aims of this study w ere to test a combination of anti-mucin antibodies to classify gastric canc er into predominant cell lineage phenotype and to determine whether MSI in GC is associated with particular cellular tumor phenotypes. Fifty-five GC w ere immunophenotyped with antibodies specific for SMC, GMC, or IC. DNA was extracted from tumor and non-neoplastic gastric tissues and amplified with 5 microsatellite markers. A mixed cellular pattern was the most frequent ph enotype of GC (61%) and was seen in both glandular (63%) and diffuse (58%)- type tumors. No significant difference in the rate of MSI was found in tumo rs with predominant gastric, intestinal or mixed phenotype. However, tumors with null or low-level expression of cellular lineage differentiation mark ers displayed MSI more frequently than tumors with high-level expression (4 0% v 20%). In conclusion, different gastric carcinoma cell lineage patterns can be easily identified with the 3 immunohistochemical markers used in th is study. The 3 main cellular lineage components of gastric cancer can be s imilarly affected by microsatellite instability, consistent with the notion that MSI is an early event in gastric carcinogenesis. Copyright (C) 2000 b y W.B. Saunders Company.