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Prognostic significance of microsatellite instability in sporadic colorectal cancer

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background and aims

Colorectal cancers exhibiting microsatellite instability (MSI) appear to have unique biological behavior. The influence of MSI on the prognosis of sporadic colorectal cancers is controversial and requires further investigation. The aim of this study was to analyze the association between MSI status and clinicopathological features and prognosis in sporadic colorectal cancer patients.

Patients and methods

Of the 322 consecutive colorectal cancer patients operated upon at the Seoul National University Hospital between January and December 1998, we examined the clinicopathological features and prognosis of 248 patients with sporadic primary colorectal cancer. The MSI status of these 248 patients has been reported in a previous study. Of the 248 patients, 23 (9.3%) had MSI+ tumors. The patients’ clinicopathological parameters were obtained from their medical records, and follow-up and survival data were obtained from medical records and phone calls.

Results

MSI+ sporadic colorectal cancers were found predominantly in the proximal colon (p<0.001) and were associated with poor differentiation (p=0.030), a lower preoperative serum carcinoembryonic antigen (CEA) level (p=0.012), and less frequent systemic metastasis (p=0.034) than MSI− tumors. Low tumor grade (p=0.022), low tumor T-stage (p=0.002), no lymph node metastasis (p<0.001), no systemic metastasis (p<0.001), adjuvant chemotherapy (p<0.001) and MSI+ status (p=0.038) were independent favorable prognostic factors for survival in sporadic colorectal cancer patients.

Conclusion

MSI status was an independent favorable prognostic factor for survival in sporadic primary colorectal cancer patients.

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References

  1. Weber JL, May PE (1989) Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet 44:388–396

    CAS  PubMed  Google Scholar 

  2. Thibodeau SN, Bren G, Schaid D (1993) Microsatellite instability in cancer of the proximal colon. Science 260:816–819

    PubMed  Google Scholar 

  3. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S (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  Google Scholar 

  4. Lynch HT, Smyrk TC, Watson P, Lanspa SJ, Lynch JF, Lynch PM, Cavalieri RJ, Boland CR (1993) Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 104:1535–1549

    CAS  PubMed  Google Scholar 

  5. Sankila R, Aaltonen LA, Jarvinen HJ, Mecklin JP (1996) Better survival rates in patients with MLH1-associated hereditary colorectal cancer. Gastroenterology 110:682–687

    CAS  PubMed  Google Scholar 

  6. Jeong SY, Shin KH, Shin JH, Ku JL, Shin YK, Park SY, Kim WH, Park J-G (2003) Microsatellite instability and mutations in DNA mismatch repair genes in sporadic colorectal cancers. Dis Colon Rectum 46:1069–1077

    PubMed  Google Scholar 

  7. Peltomaki P, Lothe RA, Aaltonen LA, Pylkkanen L, Nystrom-Lahti M, Seruca R, David L, Holm R, Ryberg D, Haugen A (1993) Microsatellite instability is associated with tumors that characterize the hereditary non-polyposis colorectal carcinoma syndrome. Cancer Res 53:5853–5855

    CAS  PubMed  Google Scholar 

  8. Aaltonen LA, Peltomaki P, Leach FS, Sistonen P, Pylkkanen L, Mecklin JP, Jarvinen H, Powell SM, Jen J, Hamilton SR, Petersen GM, Kinzler KW, Vogelstein B, Chapelle A (1993) Clues to the pathogenesis of familial colorectal cancer. Science 260:812–816

    CAS  PubMed  Google Scholar 

  9. Tannergard P, Liu T, Weger A, Nordenskjold M, Lindblom A (1997) Tumorigenesis in colorectal tumors from patients with hereditary non-polyposis colorectal cancer. Hum Genet 101:51–55

    Article  CAS  PubMed  Google Scholar 

  10. Gryfe R, Kim H, Hsieh ET, Aronson MD, Holowaty EJ, Bull SB, Redston M, Gallinger S (2000) Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 342:69–77

    CAS  PubMed  Google Scholar 

  11. Lothe RA, Peltomaki P, Meling GI, Aaltonen LA, Nystrom-Lahti M, Pylkkanen L, Heimdal K, Andersen TI, Moller P, Rognum TO, Fossa SD, Haldorsen T, Langmark F, Brogger A, Chapelle A, Borresen AL (1993) Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. Cancer Res 53:5849–5852

    CAS  PubMed  Google Scholar 

  12. Bubb VJ, Curtis LJ, Cunningham C, Dunlop MG, Carothers AD, Morris RG, White S, Bird CC, Wyllie AH (1996) Microsatellite instability and the role of hMSH2 in sporadic colorectal cancer. Oncogene 12:2641–2649

    CAS  PubMed  Google Scholar 

  13. Mass MJ, Iniesta P, Gonzalez-Quevedo R, De Juan C, Caldes T, Sanchez-Pernaute A, Cerdan J, Torres AJ, Balibrea JL, Benito M (1999) Differential prognosis of replication error phenotype and loss of heterozygosity in sporadic colorectal cancer. Eur J Cancer 35:1676–1682

    Article  PubMed  Google Scholar 

  14. Samowitz WS, Curtin K, Ma KN, Schaffer D, Coleman LW, Leppert M, Slattery ML (2001) Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level. Cancer Epidemiol Biomarkers Prev 10:917–923

    CAS  PubMed  Google Scholar 

  15. Salahshor S, Kressner U, Fischer H, Lindmark G, Glimelius B, Pahlman L, Lindblom A (1999) Microsatellite instability in sporadic colorectal cancer is not an independent prognostic factor. Br J Cancer 81:190–193

    Article  CAS  PubMed  Google Scholar 

  16. Curran B, Lenehan K, Mulcahy H, Tighe O, Bennett MA, Kay EW, O’Donoghue DP, Leader M, Croke DT (2000) Replication error phenotype, clinicopathological variables, and patient outcome in Dukes’ B stage II (T3,N0,M0) colorectal cancer. Gut 46:200–204

    Article  CAS  PubMed  Google Scholar 

  17. Feeley KM, Fullard JF, Heneghan MA, Smith T, Maher M, Murphy RP, O’Gorman TA (1999) Microsatellite instability in sporadic colorectal carcinoma is not an indicator of prognosis. J Pathol 188:14–17

    Article  CAS  PubMed  Google Scholar 

  18. Wang C, van Rijnsoever M, Grieu F, Bydder S, Elsaleh H, Joseph D, Harvey J, Iacopetta B (2003) Prognostic significance of microsatellite instability and Ki-ras mutation type in stage II colorectal cancer. Oncology 64:259–265

    Article  CAS  PubMed  Google Scholar 

  19. Park J-G, Vasen HF, Park YJ, Park KJ, Peltomaki P, de Leon MP, Rodriguez-Bigas MA, Lubinski J, Beck NE, Bisgaard ML, Miyaki M, Wijnen JT, Baba S, Lindblom A, Madlensky L, Lynch HT (2002) Suspected HNPCC and Amsterdam criteria II: evaluation of mutation detection rate, an international collaborative study. Int J Colorectal Dis 17:109–114

    Article  PubMed  Google Scholar 

  20. Greene FL, Page DL, Fleming ID, Fritz A, Balch CM, Haller DG, Morrow M (2002) AJCC cancer staging manual, 6th edn. Springer, Berlin Heidelberg New York

  21. Suh JH, Lim SD, Kim JC, Hong SH, Kang GH (2002) Comparison of clinicopathologic characteristics and genetic alterations between microsatellite instability-positive and microsatellite instability-negative sporadic colorectal carcinomas in patients younger than 40 years old. Dis Colon Rectum 45:219–228

    PubMed  Google Scholar 

  22. Johannsdottir JT, Bergthorsson JT, Gretarsdottir S, Kristjansson AK, Ragnarsson G, Jonasson JG, Egilsson V, Ingvarsson S (1999) Replication error in colorectal carcinoma: association with loss of heterozygosity at mismatch repair loci and clinicopathological variables. Anticancer Res 19:1821–1826

    CAS  PubMed  Google Scholar 

  23. Elsaleh H, Joseph D, Grieu F, Zeps N, Spry N, Iacopetta B (2000) Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet 20:1745–1750

    Article  Google Scholar 

  24. Elsaleh H, Iacopetta B (2001) Microsatellite instability is a predictive marker for survival benefit from adjuvant chemotherapy in a population-based series of stage III colorectal carcinoma. Clin Colorectal Cancer 1:104–109

    CAS  PubMed  Google Scholar 

  25. Liang JT, Huang KC, Lai HS, Lee PH, Cheng YM, Hsu HC, Cheng AL, Hsu CH, Yeh KH, Wang SM, Tang C, Chang KJ (2002) High- frequency microsatellite instability predicts better chemosensitivity to high-dose 5-fluorouracil plus leucovorin chemotherapy for stage IV sporadic colorectal cancer after palliative bowel resection. Int J Cancer 101:519-525

    Article  CAS  PubMed  Google Scholar 

  26. Halling KC, French AJ, McDonnell SK, Burgart LJ, Schaid DJ, Peterson BJ, Moon-Tasson L, Mahoney MR, Sargent DJ, O’Connell MJ, Witzig TE, Farr GH Jr, Goldberg RM, Thibodeau SN (1999) Microsatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers. J Natl Cancer Inst 91:1295–1303

    Article  CAS  PubMed  Google Scholar 

  27. De Vos WH, Meulebeld H, Kleibeuker JH, Nagengast FM, Menko FH, Griffioen G, Cats A, Morreau H, Gelderblom H, Vasen HFA (2003) Survival after adjuvant 5-FU treatment for stage III colon cancer in hereditary non polyposis colorectal cancer. Fourth Joint meeting of the LCPG and the ICG-HNPCC (Abstract F20). Familial Cancer 2:27–31

    Article  PubMed  Google Scholar 

  28. Kim H, Jen J, Vogelstein B, Hamilton SR (1994) Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol 145:148–156

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, 110-744, Seoul, Korea

    Seok-Byung Lim, Min Ro Lee & Jae-Gahb Park

  2. Cancer Research Center and Cancer Research Institute, Seoul National University, 28 Yongon-dong, Chongno-gu, 110-744, Seoul, Korea

    Seung-Yong Jeong, Ja-Lok Ku, Young-Kyoung Shin & Jae-Gahb Park

  3. Research Institute and Hospital, National Cancer Center, 809 Madu-dong, Ilsan-gu, Goyang, 411-764, Gyeonggi, Korea

    Seung-Yong Jeong & Jae-Gahb Park

  4. Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, 110-744, Seoul, Korea

    Woo Ho Kim

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  1. Seok-Byung Lim
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  2. Seung-Yong Jeong
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Correspondence to Jae-Gahb Park.

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Lim, SB., Jeong, SY., Lee, M.R. et al. Prognostic significance of microsatellite instability in sporadic colorectal cancer. Int J Colorectal Dis 19, 533–537 (2004). https://doi.org/10.1007/s00384-004-0596-2

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