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Microsatellite Instability Is Associated With a Better Prognosis for Gastric Cancer Patients After Curative Surgery

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Abstract

Background

Microsatellite instability (MSI) is one of the leading mechanisms for the carcinogenesis of gastric cancer. Its prognostic value is controversial.

Methods

Between May 1988 and Oct 2003, a total of 214 gastric cancer patients undergoing curative surgery were enrolled, and their MSI statuses were classified as MSI-H (high) or MSI-L/S (low/stable). The clinicopathologic characteristics of MSI-H and MSI-L/S gastric cancers were compared.

Results

The MSI-H tumors accounted for 11.7 % (n = 25) of the 214 total gastric cancers. Although not statistically significant, the MSI-H gastric cancers were more frequently located in the lower third of the stomach (64 % vs. 49.2 %) and were more often the intestinal type (72 % vs. 61.4 %) compared to the MSI-L/S gastric cancers. The MSI-H gastric cancers had a significantly better 5-year overall survival (OS) rate (68 % vs. 47.6 %, p = 0.030) and a trend of a better 3-year disease-free survival rate (71.8 % vs. 55.2 %, p = 0.076) compared to the MSI-L/S gastric cancers. A multivariate analysis revealed that pathologic TNM stage and MSI status were the independent prognostic factors for OS after curative surgery.

Conclusions

Compared to MSI-L/S tumors, MSI-H tumors are associated with a better OS rate for gastric cancer patients after R0 resection.

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References

  1. Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  2. Ottini L, Falchetti M, Lupi R et al (2006) Patterns of genomic instability in gastric cancer: clinical implications and perspectives. Ann Oncol 17:vii97–vii102

    Article  PubMed  Google Scholar 

  3. Oliveira C, Seruca R, Seixas M et al (1998) The clinicopathological features of gastric carcinomas with microsatellite instability may be mediated by mutations of different “target genes”: a study of the TGFbeta RII, IGFII R, and BAX genes. Am J Pathol 153:1211–1219

    Article  PubMed  CAS  Google Scholar 

  4. Gu M, Kim D, Bae Y et al (2009) Analysis of microsatellite instability, protein expression and methylation status of hMLH1 and hMSH2 genes in gastric carcinomas. Hepatogastroenterology 56:899–904

    PubMed  CAS  Google Scholar 

  5. Pedrazzani C, Corso G, Velho S et al (2009) Evidence of tumor microsatellite instability in gastric cancer with familial aggregation. Fam Cancer 8:215–220

    Article  PubMed  CAS  Google Scholar 

  6. Lee HS, Choi SI, Lee HK et al (2002) Distinct clinical features and outcomes of gastric cancers with microsatellite instability. Mod Pathol 15:632–640

    Article  PubMed  Google Scholar 

  7. Beghelli S, de Manzoni G, Barbi S et al (2006) Microsatellite instability in gastric cancer is associated with better prognosis in only stage II cancers. Surgery 139:347–356

    Article  PubMed  Google Scholar 

  8. Corso G, Pedrazzani C, Marrelli D et al (2009) Correlation of microsatellite instability at multiple loci with long-term survival in advanced gastric carcinoma. Arch Surg 144:722–727

    Article  PubMed  CAS  Google Scholar 

  9. Oki E, Kakeji Y, Zhao Y et al (2009) Chemosensitivity and survival in gastric cancer patients with microsatellite instability. Ann Surg Oncol 16:2510–2515

    Article  PubMed  Google Scholar 

  10. Seo HM, Chang YS, Joo SH et al (2009) Clinicopathologic characteristics and outcomes of gastric cancers with the MSI-H phenotype. J Surg Oncol 99:143–147

    Article  PubMed  Google Scholar 

  11. Vauhkonen M, Vauhkonen H, Sajantila A et al (2005) Differences in genomic instability between intestinal- and diffuse-type gastric cancer. Gastric Cancer 8:238–244

    Article  PubMed  CAS  Google Scholar 

  12. An JY, Kim H, Cheong JH, et al. (2011) Microsatellite instability in sporadic gastric cancer: its prognostic role and guidance for 5-FU based chemotherapy after R0 resection. Int J Cancer. doi: 10.1002/ijc.26399. [Epub ahead of print]

  13. Wu MS, Lee CW, Shun CT et al (2000) Distinct clinicopathologic and genetic profiles in sporadic gastric cancer with different mutator phenotypes. Genes Chromosomes Cancer 27:403–411

    Article  PubMed  CAS  Google Scholar 

  14. Ottini L, Palli D, Falchetti M et al (1997) Microsatellite instability in gastric cancer is associated with tumor location and family history in a high-risk population from Tuscany. Cancer Res 57:4523–4529

    PubMed  CAS  Google Scholar 

  15. Dos Santos NR, Seruca R, Constancia M et al (1996) Microsatellite instability at multiple loci in gastric carcinoma: clinicopathologic implications and prognosis. Gastroenterology 110:38–44

    Article  PubMed  Google Scholar 

  16. Chung YJ, Song JM, Lee JY et al (1996) Microsatellite instability-associated mutations associate preferentially with the intestinal type of primary gastric carcinomas in a high-risk population. Cancer Res 56:4662–4665

    PubMed  CAS  Google Scholar 

  17. Yamamoto H, Perez-Piteira J, Yoshida T et al (1999) Gastric cancers of the microsatellite mutator phenotype display characteristic genetic and clinical features. Gastroenterology 116:1348–1357

    Article  PubMed  CAS  Google Scholar 

  18. Buonsanti G, Calistri D, Padovan L et al (1997) Microsatellite instability in intestinal- and diffuse-type gastric carcinoma. J Pathol 182:167–173

    Article  PubMed  CAS  Google Scholar 

  19. De Manzoni G, Tomezzoli A, Di Leo A et al (2001) Clinical significance of mutator phenotype and chromosome 17p and 18q allelic loss in gastric cancer. Br J Surg 88:419–425

    Article  PubMed  Google Scholar 

  20. Gazvoda B, Juvan R, Zupanic-Pajnic I et al (2007) Genetic changes in Slovenian patients with gastric adenocarcinoma evaluated in terms of microsatellite DNA. Eur J Gastroenterol Hepatol 19:1082–1089

    Article  PubMed  CAS  Google Scholar 

  21. Hayden JD, Cawkwell L, Quirke P et al (1997) Prognostic significance of microsatellite instability in patients with gastric carcinoma. Eur J Cancer 33:2342–2346

    Article  PubMed  CAS  Google Scholar 

  22. Schneider BG, Bravo JC, Roa JC et al (2000) Microsatellite instability, prognosis and metastasis in gastric cancers from a low-risk population. Int J Cancer 89:444–452

    Article  PubMed  CAS  Google Scholar 

  23. An C, Choi IS, Yao JC et al (2005) Prognostic significance of CpG island methylator phenotype and microsatellite instability in gastric carcinoma. Clin Cancer Res 11:656–663

    PubMed  CAS  Google Scholar 

  24. Perez RO, Jacob CE, D’Ottaviano FL et al (2004) Microsatellite instability in solitary and sporadic gastric cancer. Rev Hosp Clin Fac Med Sao Paulo 59:279–285

    Article  PubMed  Google Scholar 

  25. Sobin L, Gospodarowicz M, Wittekind C (eds) (2009) TNM Classification of Malignant Tumours, 7th edn. International Union Against Cancer (UICC), Wiley, New York

    Google Scholar 

  26. Sakuramoto S, Sasako M, Yamaguchi T et al (2007) ACTS-GC Group: adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357:1810–1820

    Article  PubMed  CAS  Google Scholar 

  27. Boland CR, Thibodeau SN, Hamilton SR et al (1998) A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257

    PubMed  CAS  Google Scholar 

  28. Chang SC, Lin JK, Yang SH et al (2006) Relationship between genetic alterations and prognosis in sporadic colorectal cancer. Int J Cancer 118:1721–1727

    Article  PubMed  CAS  Google Scholar 

  29. Raut CP, Pawlik TM, Rodriguez-Bigas MA (2004) Clinicopathologic features in colorectal cancer patients with microsatellite instability. Mutat Res 568:275–282

    Article  PubMed  CAS  Google Scholar 

  30. Söreide K, Janssen EA, Söiland H et al (2006) Microsatellite instability in colorectal cancer. Br J Surg 93:395–406

    Article  PubMed  Google Scholar 

  31. Markowitz SD, Wang J, Myeroff L et al (1995) Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 268:1336–1338

    Article  PubMed  CAS  Google Scholar 

  32. Souza RE, Appel R, Yin J et al (1996) Microsatellite instability in the insulin-like growth factor II receptor gene in gastrointestinal tumours. Nature Genet 14:255–257

    Article  PubMed  CAS  Google Scholar 

  33. Souza RF, Yin J, Smolinski KN et al (1997) Frequent mutation of the E2F-4 cell cycle gene in primary human gastrointestinal tumors. Cancer Res 57:2350–2353

    PubMed  CAS  Google Scholar 

  34. Rampino N, Yamamoto H, Ionov Y et al (1997) Somatic mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science 275:967–969

    Article  PubMed  CAS  Google Scholar 

  35. Schwartz S Jr, Yamamoto H, Navarro M et al (1999) Frameshift mutations at mononucleotide repeats in caspase-5 and other target genes in endometrial and gastrointestinal cancer of the microsatellite mutator phenotype. Cancer Res 59:2995–3002

    PubMed  CAS  Google Scholar 

  36. Riccio A, Aaltonen LA, Godwin AK et al (1999) The DNA repair gene MBD4 (MED1) is mutated in human carcinomas with microsatellite instability. Nat Genet 23:266–268

    Article  PubMed  CAS  Google Scholar 

  37. Fiocca R, Luinetti O, Villani L et al (2001) Molecular mechanisms involved in the pathogenesis of gastric carcinoma: interactions between genetic alterations, cellular phenotype and cancer histotype. Hepatogastroenterology 48:1523–1530

    PubMed  CAS  Google Scholar 

  38. El-Rifai W, Powell SM (2002) Molecular biology of gastric cancer. Semin Radiat Oncol 12:128–140

    Article  PubMed  Google Scholar 

  39. Toyota M, Ahuja N, Suzuki H et al (1999) Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res 59:5438–5442

    PubMed  CAS  Google Scholar 

  40. Lee JH, Park SJ, Abraham SC et al (2004) Frequent CpG island methylation in precursor lesions and early gastric adenocarcinomas. Oncogene 23:4646–4654

    Article  PubMed  CAS  Google Scholar 

  41. Leung WK, Yu J, Ng EK et al (2001) Concurrent hypermethylation of multiple tumor-related genes in gastric carcinoma and adjacent normal tissues. Cancer 91:2294–2301

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by the Center of Excellence for Cancer Research at Taipei Veterans General Hospital (DOH101-TD-C-111-007) and funding from the National Science Council (99-2314-B-075-009).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

    Wen-Liang Fang, Kuo-Hung Huang & Chew-Wun Wu

  2. Division of Colorectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

    Shih-Ching Chang & Yuan-Tzu Lan

  3. National Yang-Ming University, Taipei, Taiwan

    Shih-Ching Chang, Kuo-Hung Huang, Jen-Hao Chen, Su-Shun Lo, Anna Fen-Yau Li & Chew-Wun Wu

  4. Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Wen-Liang Fang, Yuan-Tzu Lan & Shih-Hwa Chiou

  5. National Yang-Ming University Hospital, Ilan, Taiwan

    Su-Shun Lo

  6. Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan

    Anna Fen-Yau Li

  7. En Chu Kong Hospital, Taipei, Taiwan

    Jen-Hao Chen

  8. Taipei Medical College-Affiliated Taipei Municipal Wan-Fang Hospital, Taipei, Taiwan

    Mao-Chih Hsieh

  9. Department of Medical Research and Education, Taipei Veterans General Hospital, 201 Section 2, Shih-Pai Road, Taipei, 11217, Taiwan

    Shih-Hwa Chiou

  10. Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan

    Shih-Hwa Chiou

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  1. Wen-Liang Fang
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Correspondence to Shih-Hwa Chiou.

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Fang, WL., Chang, SC., Lan, YT. et al. Microsatellite Instability Is Associated With a Better Prognosis for Gastric Cancer Patients After Curative Surgery. World J Surg 36, 2131–2138 (2012). https://doi.org/10.1007/s00268-012-1652-7

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  • DOI: https://doi.org/10.1007/s00268-012-1652-7

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