title: Stage IV early gastric cancer: two cases with microsatellite instability.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ji Yeong
authors.initials: JY
authors.lastname: An
authors.forename: Min Gew
authors.initials: MG
authors.lastname: Choi
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Noh
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
authors.forename: Dae Sik
authors.initials: DS
authors.lastname: Kim
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Sohn
authors.forename: Sung
authors.initials: S
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000368:Aged; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000473:pathology; D003131:Combined Modality Therapy; D019175:DNA Methylation; D053843:DNA Mismatch Repair; D005743:Gastrectomy; D005753:Gastric Mucosa / Q000473:pathology; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D011706:Pyloric Antrum / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1