Stage IV early gastric cancer: two cases with microsatellite instability.

BACKGROUND

We experienced two rare cases of stage IV early gastric carcinoma with extensive lymph node metastasis (pT1N3) and microsatellite instability caused by methylation of the MLH1 gene.

MATERIALS AND

METHODS

The clinicopathological features of patients with stage IV EGC were examined. Microsatellite instability (MSI) was analyzed using five microsatellite markers and MLH1 gene promoter methylation patterns were determined by methylation specific polymerase chain reaction (PCR) from paraffin-embedded tissue samples. Loss of hMLH1 was identified by immunohistochemical study.

RESULTS

In both cases, the carcinomas were located in the antrum of the stomach, confined within the submucosa (SM3) and accompanied by endolymphatic tumor emboli. Immunohistochemical analysis for hMLH1 showed negative nuclear staining in the carcinoma cells. The tumor demonstrated methylation of the MLH1 gene and MSI-H because they manifested instability in three and two of the five markers tested. One patient is alive without any clinical, radiological, or pathological evidence of recurrence or metastasis at 37 months, while the other patient died after a cerebrovascular accident 5 months after surgery.

CONCLUSION

Our rare cases support that MSI caused by MLH1 promoter methylation and the loss of hMLH1 protein play an important role in stage IV EGC development.