[Microsatellite instability in gastric cancer with varied structure]

The intratumoral histological heterogeneity of cancer has been investigated by many pathologists. Although microsatellite alteration has been reported in gastric cancer, the significance of genomic instability in these histologically heterogeneous cases has not been elucidated.

Microsatellite alteration detected by polymerase chain reaction (PCR) in 13 primary advanced gastric cancers with varied structure was examined at 8 microsatellite loci.

We were able to detect a greater prevalence of replication errors (RER) (6/13, 46.2%) at the primary site of gastric cancer than previously reported and loss of heterozygosity (LOH) at 17p (4/13, 30.8%) was demonstrated at the primary sites. All the same time, we also examined metastatic tumors in the regional lymph nodes in 12 of these cases. The frequency of RER (8/12, 66.7%) in metastatic lesions was higher than that in primary tumors. Detectability of RER was more frequent in the poorly differentiated portions than the well-differentiated portions of lymph node metastases.

These findings suggest that gastric cancer with varied structure acquired frequent microsatellite instability during progression and metastasis, and we reasoned that the mutator phenotype detected by microsatellite alterations may represent heterogeneous tumor clones in gastric cancer and lymph node metastases.