The assessment of microsatellite instability (MSI) is not included yet in the routine evaluation of patients with gastric cancer, as controversial data exist regarding its prognostic value.
We determined the clinical significance of MSI in 510 sporadic gastric cancers, using the mononucleotide markers BAT25 and BAT26. The results were compared with the immunohistochemical expression of the mismatch repair proteins Mlh1 and Msh2.
MSI was present in 83 (16%) cancers and correlated with better survival (P < .001). Multivariate analysis showed that the MSI phenotype was an independent factor (P = .005) and added prognostic information to TNM stage, location, and age. The relative risk of death for MSI cancer patients was 0.6 (95% confidence interval [CI], 0.4-0.8). Moreover, when grouped according to stage, only stage II cancers showed a significant effect of MSI status on survival (P = .011; hazard ratio = 0.3; 95% CI, 0.1-0.8). MSI also correlated with older age (P = .002), female gender (P < .001), intestinal histotype (P = .011), lower T stage (P = .018), and less lymph node involvement (P < .001). Finally, comparison of the results of immunohistochemical expression of the mismatch repair proteins Mlh1 and Msh2 with microsatellite analysis showed concordant results in 95% of neoplasms, with a sensitivity of 82% and specificity of 98%.
Microsatellite analysis of gastric cancer has clinical utility in determination of prognosis, but should be determined in only stage II neoplasms in a routine clinical setting. Immunohistochemistry may be considered sufficient, although microsatellite analysis is preferable.
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- Cancer statistics, 2002.CA Cancer J Clin. 2002; 52: 23-47
- Surgical approaches and outcomes in the treatment of gastric cancer.Semin Radiat Oncol. 2002; 12: 162-169
- Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction.N Engl J Med. 2001; 345: 725-730
- Microsatellite instability.Nat Med. 1996; 2: 630-631
- Gastric cancers of the microsatellite mutator phenotype display characteristic genetic and clinical features.Gastroenterology. 1999; 116: 1348-1357
- Microsatellite instability as a tool for the classification of gastric cancer.Trends Mol Med. 2001; 7: 76-80
- Frequency and prognostic impact of microsatellite instability in a large population-based study of endometrial carcinomas.Cancer Res. 2000; 60: 1750-1752
- Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas.Am J Pathol. 2000; 156: 1641-1651
- DNA markers predicting benefit from adjuvant fluorouracil in patients with colon cancer.Lancet. 2002; 360: 1381-1391
- Prognostic significance of microsatellite instability determined by immunohistochemical staining of MSH2 and MLH1 in sporadic T3N0M0 colon cancer.Gut. 2004; 53: 371-375
- Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer.N Engl J Med. 2003; 349: 247-257
- Clinical significance of mutator phenotype and chromosome 17p and 18q allelic loss in gastric cancer.Br J Surg. 2001; 88: 419-425
- Microsatellite instability at multiple loci in gastric carcinoma.Gastroenterology. 1996; 110: 38-44
- Microsatellite instability and loss of heterozygosity in gastric carcinoma in comparison to family history.Am J Pathol. 1998; 152: 1281-1289
- Prognostic significance of CpG island methylator phenotype and microsatellite instability in gastric carcinoma.Clin Cancer Res. 2005; 11: 656-663
- Prognostic implications of microsatellite genotypes in gastric carcinoma.Int J Cancer. 2000; 89: 378-383
- Alterations of BAT-26 identify a subset of gastric cancer with distinct clinicopathologic features and better postoperative prognosis.Hepatogastroenterology. 2002; 49: 285-289
- Distinct clinical features and outcomes of gastric cancers with microsatellite instability.Mod Pathol. 2002; 15: 632-640
- The Two Histological Main Types Of Gastric Carcinoma.Acta Pathol Microbiol Scand. 1965; 64: 31-49
- Classification of malignant tumours. 4th ed. Springer, Berlin1992
- Molecular characterization of pancreatic serous microcystic adenomas.Am J Pathol. 2001; 158: 317-321
- Frequency of loss of hMLH1 expression in colorectal carcinoma increases with advancing age.Cancer. 2003; 97: 1421-1427
- Relationship between MUC5AC and altered expression of MLH1 protein in mucinous and non-mucinous colorectal carcinomas.Pathol Res Pract. 2004; 200: 371-377
- A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition.Cancer Res. 1998; 58: 5248-5257
- A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition.Cancer Res. 1999; 59 (Correspondence re): 249-256
- Origin of microsatellite instability in gastric cancer.Am J Pathol. 1999; 155: 205-211
- Microsatellite instability, Epstein-Barr virus, mutation of type II transforming growth factor beta receptor and BAX in gastric carcinomas in Hong Kong Chinese.Br J Cancer. 1999; 79: 582-588
- The clinicopathological features of gastric carcinomas with microsatellite instability may be mediated by mutations of different “target genes”.Am J Pathol. 1998; 153: 1211-1219
- The role of microsatellite instability in gastric carcinoma.Gut. 1998; 42: 300-303
- Age-related hypermethylation of the hMLH1 promoter in gastric cancers.Int J Cancer. 2001; 94: 208-211
- Frequent CpG island methylation in precursor lesions and early gastric adenocarcinomas.Oncogene. 2004; 23: 4646-4654
- Allelic imbalance of 8p indicates poor survival in gastric cancer.J Mol Diagn. 2004; 6: 243-252
- Microsatellite instability in adenocarcinomas of the upper gastrointestinal tract. Relation to clinicopathological data and family history.Am J Pathol. 1995; 147: 593-600
- Expression of hMLH1 is inactivated in the gastric adenomas with enhanced microsatellite instability.Br J Cancer. 2001; 85: 1147-1152
- Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences.Virchows Arch. 2001; 438: 39-48
- hMLH1 promoter methylation and lack of hMLH1 expression in sporadic gastric carcinomas with high-frequency microsatellite instability.Cancer Res. 1999; 59: 159-164
- Correlation of mismatch repair genes immunohistochemistry and microsatellite instability status in HNPCC-associated tumours.Pathology. 2002; 34: 541-547
- Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors.J Clin Oncol. 2002; 20: 1043-1048
- Role of DNA mismatch repair defects in the pathogenesis of human cancer.J Clin Oncol. 2003; 21: 1174-1179
- Microsatellite instability in colorectal cancer.Cancer Res. 1998; 58: 1713-1718
- Molecular and clinical characteristics of MSH6 variants.Am J Hum Genet. 2002; 70: 26-37
- Current treatments and future perspectives in colorectal and gastric cancer.Ann Oncol. 2003; 14 (ii49-55)
- Preoperative genetic diagnosis of gastric carcinoma based on chromosomal loss and microsatellite instability.Int J Cancer. 2005; 113: 249-258
Accepted: August 29, 2005Verona, Siena, Carpi, and Forli, Italy
Supported by Fondazione Cassa di Risparmio di Verona (Bando 2004) to P. S. Moore; Associazione Italiana Ricerca sul Cancro (AIRC), Milan, Italy to G. de Manzoni; CNR-MIUR, Rome, Italy.
© 2006 Mosby, Inc. Published by Elsevier Inc. All rights reserved.