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.


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.
An
Ji Yeong
JY
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Choi
Min Gew
MG
Noh
Jae Hyung
JH
Kim
Kyoung-Mee
KM
Kim
Dae Sik
DS
Sohn
Tae Sung
TS
Kim
Sung
S
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
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1