Skip to main content
Top
Published in: International Journal of Colorectal Disease 6/2004

01-11-2004 | Original Article

Prognostic significance of microsatellite instability in sporadic colorectal cancer

Authors: Seok-Byung Lim, Seung-Yong Jeong, Min Ro Lee, Ja-Lok Ku, Young-Kyoung Shin, Woo Ho Kim, Jae-Gahb Park

Published in: International Journal of Colorectal Disease | Issue 6/2004

Login to get access

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.
Literature
1.
go back to reference Weber JL, May PE (1989) Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet 44:388–396PubMed Weber JL, May PE (1989) Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet 44:388–396PubMed
2.
go back to reference Thibodeau SN, Bren G, Schaid D (1993) Microsatellite instability in cancer of the proximal colon. Science 260:816–819PubMed Thibodeau SN, Bren G, Schaid D (1993) Microsatellite instability in cancer of the proximal colon. Science 260:816–819PubMed
3.
go back to reference 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 58:5248–5257PubMed 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 58:5248–5257PubMed
4.
go back to reference 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 104:1535–1549PubMed 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 104:1535–1549PubMed
5.
go back to reference Sankila R, Aaltonen LA, Jarvinen HJ, Mecklin JP (1996) Better survival rates in patients with MLH1-associated hereditary colorectal cancer. Gastroenterology 110:682–687PubMed Sankila R, Aaltonen LA, Jarvinen HJ, Mecklin JP (1996) Better survival rates in patients with MLH1-associated hereditary colorectal cancer. Gastroenterology 110:682–687PubMed
6.
go back to reference 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 46:1069–1077PubMed 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 46:1069–1077PubMed
7.
go back to reference 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 53:5853–5855PubMed 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 53:5853–5855PubMed
8.
go back to reference 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 260:812–816PubMed 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 260:812–816PubMed
9.
go back to reference 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 101:51–55CrossRefPubMed 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 101:51–55CrossRefPubMed
10.
go back to reference 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 342:69–77PubMed 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 342:69–77PubMed
11.
go back to reference 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 53:5849–5852PubMed 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 53:5849–5852PubMed
12.
go back to reference 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 12:2641–2649PubMed 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 12:2641–2649PubMed
13.
go back to reference 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 35:1676–1682CrossRefPubMed 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 35:1676–1682CrossRefPubMed
14.
go back to reference 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 10:917–923PubMed 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 10:917–923PubMed
15.
go back to reference 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 81:190–193CrossRefPubMed 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 81:190–193CrossRefPubMed
16.
go back to reference 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 46:200–204CrossRefPubMed 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 46:200–204CrossRefPubMed
17.
go back to reference 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 188:14–17CrossRefPubMed 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 188:14–17CrossRefPubMed
18.
go back to reference 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 64:259–265CrossRefPubMed 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 64:259–265CrossRefPubMed
19.
go back to reference 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 17:109–114CrossRefPubMed 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 17:109–114CrossRefPubMed
20.
go back to reference 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 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.
go back to reference 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 45:219–228PubMed 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 45:219–228PubMed
22.
go back to reference 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 19:1821–1826PubMed 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 19:1821–1826PubMed
23.
go back to reference 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 20:1745–1750CrossRef 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 20:1745–1750CrossRef
24.
go back to reference 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 1:104–109PubMed 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 1:104–109PubMed
25.
go back to reference 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 101:519-525CrossRefPubMed 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 101:519-525CrossRefPubMed
26.
go back to reference 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 91:1295–1303CrossRefPubMed 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 91:1295–1303CrossRefPubMed
27.
go back to reference 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 2:27–31CrossRefPubMed 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 2:27–31CrossRefPubMed
28.
go back to reference 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 145:148–156PubMed 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 145:148–156PubMed
Metadata
Title
Prognostic significance of microsatellite instability in sporadic colorectal cancer
Authors
Seok-Byung Lim
Seung-Yong Jeong
Min Ro Lee
Ja-Lok Ku
Young-Kyoung Shin
Woo Ho Kim
Jae-Gahb Park
Publication date
01-11-2004
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 6/2004
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-004-0596-2

Other articles of this Issue 6/2004

International Journal of Colorectal Disease 6/2004 Go to the issue