Clinicopathologic characteristics and outcomes of gastric cancers with the MSI-H phenotype.
OBJECTIVE
We examined the correlation between microsatellite instability (MSI) status and the clinicopathological features and prognostic value in gastric cancer and compared the efficacy of immunohistochemical staining for hMLH1 and hMSH2 with a polymerase chain reaction (PCR)-based test.


METHODS
MSI status was examined in 328 consecutive gastric adenocarcinomas using tissue preserved in paraffin blocks. DNA extracted from tumor sections and the corresponding normal tissue was analyzed using PCR at the five microsatellite loci recommended by the National Cancer Institute (NCI). Immunohistochemical staining for hMLH1 and hMSH2 was performed and the results were compared with the MSI status measured using PCR. The relationship of the clinicopathologic variables to MSI status was analyzed.


RESULTS
Of the gastric cancers, 8.2% (n = 27) contained MSI-H and this was associated with older age (>70 years), distal tumor location, tumor size, and intestinal subtype. Lymphatic and vascular invasion were associated with the disease-free survival. On immunohistochemical staining, the loss of expression of hMLH1 or hMSH2 was observed in 11% (n = 36). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of immunohistochemical staining were 63.0%, 93.7%, 47.2%, 96.6%, and 91.2%, respectively.


CONCLUSIONS
Gastric cancers with MSI-H have specific clinicopathologic characteristics, such as older age at diagnosis, distal tumor location, increased tumor size, and intestinal histologic type. However, immunohistochemical staining for hMLH1 and hMSH2 is not as accurate as the PCR-based MSI test.
Seo
Hyung Min
HM
Department of Surgery, Kyung Hee University College of Medicine, Seoul, Korea.
Chang
Yeon Soo
YS
Joo
Sun Hyung
SH
Kim
Youn Wha
YW
Park
Yong-Koo
YK
Hong
Sung Wha
SW
Lee
Suk-Hwan
SH
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D000368:Aged; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012680:Sensitivity and Specificity; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein