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

Gastric carcinomas (GC) are heterogeneous tumors comprising variable amounts of cells of different lineage phenotype, including gastric mucous cells (surface--SMC or gland--GMC) and intestinal cells (IC). The evaluation of tumor behavior has classically depended on strictly morphological classifications of tumors. Microsatellite instability (MSI) is frequently detected in GC, but whether MSI affects all gastric cellular lineages or exclusively occurs in unique cellular lineages in GC is not known. The aims of this study were to test a combination of anti-mucin antibodies to classify gastric cancer into predominant cell lineage phenotype and to determine whether MSI in GC is associated with particular cellular tumor phenotypes. Fifty-five GC were 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 phenotype 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 tumors with predominant gastric, intestinal or mixed phenotype. However, tumors with null or low-level expression of cellular lineage differentiation markers displayed MSI more frequently than tumors with high-level expression (40% v 20%). In conclusion, different gastric carcinoma cell lineage patterns can be easily identified with the 3 immunohistochemical markers used in this study. The 3 main cellular lineage components of gastric cancer can be similarly affected by microsatellite instability, consistent with the notion that MSI is an early event in gastric carcinogenesis.