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.
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.
Authors: A M Chiaravalli; M Cornaggia; D Furlan; C Capella; R Fiocca; G Tagliabue; C Klersy; E Solcia Journal: Virchows Arch Date: 2001-08 Impact factor: 4.064
Authors: A S Fleisher; M Esteller; S Wang; G Tamura; H Suzuki; J Yin; T T Zou; J M Abraham; D Kong; K N Smolinski; Y Q Shi; M G Rhyu; S M Powell; S P James; K T Wilson; J G Herman; S J Meltzer Journal: Cancer Res Date: 1999-03-01 Impact factor: 12.701
Authors: Won Hyuk Choe; Sun-Young Lee; Jun Haeng Lee; Sang Goon Shim; Young-Ho Kim; Poong-Lyul Rhee; Jong Chul Rhee; Chang-Seok Ki; Jong-Won Kim; Sang Yong Song; Jae J Kim Journal: Korean J Intern Med Date: 2005-06 Impact factor: 2.884