Microsatellite instability screening and clinical efficacy in tumor tissue in patients with colorectal cancer
Abstract
Aim:
Microsatellite instability is a genetic pathway responsible for approximately
15% of sporadic colon cancers. It is caused by defects in the DNA mismatch
repair system. Microsatellite instability occurs in people with a damaged DNA
mismatch repair system and the risk of mutation increases. These
mutations in tumor suppressor genes cause colorectal cancer development.
Microsatellite instability is most commonly detected in proximal colon cancers.
Microsatellite instability in cancer tissues can be determined by PCR method.
In our group of patients with colorectal cancer, we planned a study to
investigate the effect of microsatellite instability on the clinicopathological
features and prognosis. Methods: In
this study, microsatellite instability was investigated in 50 patients who were
diagnosed to have colorectal cancer in Çukurova University Medical Faculty
Hospital. Results: Paraffin-embedded
specimens were examined by PCR method and 20 (40%) of them were
‘’microsatellite instable’’ and 30 (60%) were ‘’microsatellite stable’’. In
cases with microsatellite instability, tumors were found to be more proximal in
the proximal colon than in microsatellite stable cases (40% to 13.3%,
respectively, p <0.05). The age at the time of diagnosis was found younger
in the microsatellite instable group compared to the microsatellite stable
group (52.2 versus 61.97 years, respectively). Conclusion: The fact that microsatellite instable colorectal tumors
are different from those of microsatellite stable in terms of clinicopathological
and prognostic aspects suggests that this feature can be used as a prognostic
marker in the future. Further studies
with more cases are needed.
References
- 1. Gill, S., R.R. Thomas, and R.M. Goldberg, Review article: colorectal cancer chemotherapy. Aliment Pharmacol Ther, 2003. 18(7): p. 683-92.
- 2. Compton, C.C. and F.L. Greene, The staging of colorectal cancer: 2004 and beyond. CA Cancer J Clin, 2004. 54(6): p. 295-308.
- 3. Gryfe, R., et al., Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med, 2000. 342(2): p. 69-77.
- 4. Narayan, S. and D. Roy, Role of APC and DNA mismatch repair genes in the development of colorectal cancers. Mol Cancer, 2003. 2: p. 41.
- 5. Bisgaard, M.L., et al., Familial adenomatous polyposis patients without an identified APC germline mutation have a severe phenotype. Gut, 2004. 53(2): p. 266-70.6. Lindblom, A., Different mechanisms in the tumorigenesis of proximal and distal colon cancers. Curr Opin Oncol, 2001. 13(1): p. 63-9.
- 7. Tejpar, S. and E. Van Cutsem, Molecular and genetic defects in colorectal tumorigenesis. Best Pract Res Clin Gastroenterol, 2002. 16(2): p. 171-85.
- 8. Sevignani, C., et al., Tumorigenic conversion of p53-deficient colon epithelial cells by an activated Ki-ras gene. J Clin Invest, 1998. 101(8): p. 1572-80.
- 9. Carethers, J.M., et al., Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer. Gastroenterology, 2004. 126(2): p. 394-401.
- 10. De' Angelis, G.L., et al., Microsatellite instability in colorectal cancer. Acta Biomed, 2018. 89(9-s): p. 97-101.
- 11. Lawes, D.A., S. SenGupta, and P.B. Boulos, The clinical importance and prognostic implications of microsatellite instability in sporadic cancer. Eur J Surg Oncol, 2003. 29(3): p. 201-12.
- 12. Wheeler, J.M., W.F. Bodmer, and N.J. Mortensen, DNA mismatch repair genes and colorectal cancer. Gut, 2000. 47(1): p. 148-53.
- 13. Wynter, C.V., et al., Methylation patterns define two types of hyperplastic polyp associated with colorectal cancer. Gut, 2004. 53(4): p. 573-80.
- 14. Umar, A., et al., Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst, 2004. 96(4): p. 261-8.
- 15. Jass, J.R., HNPCC and sporadic MSI-H colorectal cancer: a review of the morphological similarities and differences. Fam Cancer, 2004. 3(2): p. 93-100.
- 16. Ribic, C.M., et al., Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med, 2003. 349(3): p. 247-57.
- 17. Parc, Y., et al., Prognostic significance of microsatellite instability determined by immunohistochemical staining of MSH2 and MLH1 in sporadic T3N0M0 colon cancer. Gut, 2004. 53(3): p. 371-5.
- 18. Meyers, M., et al., Role of DNA mismatch repair in apoptotic responses to therapeutic agents. Environ Mol Mutagen, 2004. 44(4): p. 249-64.
- 19. Ilyas, M., et al., Genetic pathways in colorectal and other cancers. Eur J Cancer, 1999. 35(14): p. 1986-2002.
- 20. Haydon, A.M. and J.R. Jass, Emerging pathways in colorectal-cancer development. Lancet Oncol, 2002. 3(2): p. 83-8.
- 21. Jenkins, M.A., et al., Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study. Gastroenterology, 2007. 133(1): p. 48-56.
- 22. Hampel, H., et al., Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med, 2005. 352(18): p. 1851-60.
- 23. Nowak, M.A., et al., The role of chromosomal instability in tumor initiation. Proc Natl Acad Sci U S A, 2002. 99(25): p. 16226-31.
- 24. Watanabe, T., et al., Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med, 2001. 344(16): p. 1196-206.
- 25. Kurzawski, G., et al., Importance of microsatellite instability (MSI) in colorectal cancer: MSI as a diagnostic tool. Ann Oncol, 2004. 15 Suppl 4: p. iv283-4.
- 26. Halling, K.C., et al., Microsatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers. J Natl Cancer Inst, 1999. 91(15): p. 1295-303.
- 27. Kim, H., et al., Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol, 1994. 145(1): p. 148-56.
- 28. Thibodeau, S.N., et al., Microsatellite instability in colorectal cancer: different mutator phenotypes and the principal involvement of hMLH1. Cancer Res, 1998. 58(8): p. 1713-8.
- 29. Cunningham, J.M., et al., Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res, 1998. 58(15): p. 3455-60.
- 30. Kahlenberg, M.S., et al., Molecular prognostics in colorectal cancer. Surg Oncol, 2003. 12(3): p. 173-86.
Kolorektal kanserli hastalarda tümör dokusunda mikrosatellit instabilite taranması ve klinik üzerine etkinliği
Abstract
Amaç: Mikrosatellit
instabilite, sporadik kolon kanserlerinin yaklaşık %15’inden sorumlu bir
genetik yolaktır. DNA mismatch (hatalı eşleşme) onarım sistemindeki
defektlerden dolayı oluşmaktadır. DNA mismatch onarım sistemi hatalı olan
kişilerde mikrosatellit instabilite oluşmakta ve mutasyon riski artmaktadır.
Tümör süpresör genlerde oluşan bu mutasyonlar başta kolorektal
kanser olmak üzere, endometrium kanseri, gastrik kanser vb malignansilerin
gelişimine yol açmaktadır. Mikrosatellit instabilite en sık proksimal kolon
kanserlerinde saptanmaktadır. Kanser dokularında mikrosatellit instabilite, PCR
yöntemi ile saptanabilmektedir. Kliniğimizde tanı koyulan kolorektal kanserli
hasta grubumuzda, Mikrosatellit İnstabilitenin klinikopatolojik özellikleri ve
prognoz üzerine etkisini araştırmak üzere bir çalışma planladık. Yöntem: Bu çalışmada Çukurova
Üniversitesi Tıp Fakültesi Hastanesi’nde tanı almış kolorektal kanserli 50
hastadan elde edilen kanserli parafin doku örneklerinde mikrosatellit
instabilite aranmıştır. Bulgular:
Parafine gömülü örneklerin PCR yöntemiyle incelenmesi sonucunda hastaların
20’si (%40) mikrosatellit instabil, 30’u (%60) mikrosatellit stabil olarak
saptandı. Mikrosatellit instabil olan olgularda, mikrosatellit stabil olgulara
göre daha sık oranda tümörlerin proksimal kolonda yerleştiği saptandı
(sırasıyla %40’a karşılık %13.3, p<0.05). Mikrosatellit instabil grupla
mikrosatelit stabil grup, tanı sırasındaki yaş açısından karşılaştırıldığında, instabil
olanlarda tanı sırasındaki yaşın daha küçük olduğu saptandı (sırasıyla 52.2’ye
karşılık 61.97 yaş). Sonuç:
Mikrosatellit instabil kolorektal tümörlerin klinikopatolojik ve prognostik
açıdan mikrosatellit stabil olanlardan farklı olması, ileride bu özelliğin
prognostik bir belirteç olarak kullanılabileceğini düşündürmektedir. Konuyla
ilgili daha fazla olgu sayılarıyla yeni çalışmalara ihtiyaç vardır.
References
- 1. Gill, S., R.R. Thomas, and R.M. Goldberg, Review article: colorectal cancer chemotherapy. Aliment Pharmacol Ther, 2003. 18(7): p. 683-92.
- 2. Compton, C.C. and F.L. Greene, The staging of colorectal cancer: 2004 and beyond. CA Cancer J Clin, 2004. 54(6): p. 295-308.
- 3. Gryfe, R., et al., Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med, 2000. 342(2): p. 69-77.
- 4. Narayan, S. and D. Roy, Role of APC and DNA mismatch repair genes in the development of colorectal cancers. Mol Cancer, 2003. 2: p. 41.
- 5. Bisgaard, M.L., et al., Familial adenomatous polyposis patients without an identified APC germline mutation have a severe phenotype. Gut, 2004. 53(2): p. 266-70.6. Lindblom, A., Different mechanisms in the tumorigenesis of proximal and distal colon cancers. Curr Opin Oncol, 2001. 13(1): p. 63-9.
- 7. Tejpar, S. and E. Van Cutsem, Molecular and genetic defects in colorectal tumorigenesis. Best Pract Res Clin Gastroenterol, 2002. 16(2): p. 171-85.
- 8. Sevignani, C., et al., Tumorigenic conversion of p53-deficient colon epithelial cells by an activated Ki-ras gene. J Clin Invest, 1998. 101(8): p. 1572-80.
- 9. Carethers, J.M., et al., Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer. Gastroenterology, 2004. 126(2): p. 394-401.
- 10. De' Angelis, G.L., et al., Microsatellite instability in colorectal cancer. Acta Biomed, 2018. 89(9-s): p. 97-101.
- 11. Lawes, D.A., S. SenGupta, and P.B. Boulos, The clinical importance and prognostic implications of microsatellite instability in sporadic cancer. Eur J Surg Oncol, 2003. 29(3): p. 201-12.
- 12. Wheeler, J.M., W.F. Bodmer, and N.J. Mortensen, DNA mismatch repair genes and colorectal cancer. Gut, 2000. 47(1): p. 148-53.
- 13. Wynter, C.V., et al., Methylation patterns define two types of hyperplastic polyp associated with colorectal cancer. Gut, 2004. 53(4): p. 573-80.
- 14. Umar, A., et al., Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst, 2004. 96(4): p. 261-8.
- 15. Jass, J.R., HNPCC and sporadic MSI-H colorectal cancer: a review of the morphological similarities and differences. Fam Cancer, 2004. 3(2): p. 93-100.
- 16. Ribic, C.M., et al., Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med, 2003. 349(3): p. 247-57.
- 17. Parc, Y., et al., Prognostic significance of microsatellite instability determined by immunohistochemical staining of MSH2 and MLH1 in sporadic T3N0M0 colon cancer. Gut, 2004. 53(3): p. 371-5.
- 18. Meyers, M., et al., Role of DNA mismatch repair in apoptotic responses to therapeutic agents. Environ Mol Mutagen, 2004. 44(4): p. 249-64.
- 19. Ilyas, M., et al., Genetic pathways in colorectal and other cancers. Eur J Cancer, 1999. 35(14): p. 1986-2002.
- 20. Haydon, A.M. and J.R. Jass, Emerging pathways in colorectal-cancer development. Lancet Oncol, 2002. 3(2): p. 83-8.
- 21. Jenkins, M.A., et al., Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study. Gastroenterology, 2007. 133(1): p. 48-56.
- 22. Hampel, H., et al., Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med, 2005. 352(18): p. 1851-60.
- 23. Nowak, M.A., et al., The role of chromosomal instability in tumor initiation. Proc Natl Acad Sci U S A, 2002. 99(25): p. 16226-31.
- 24. Watanabe, T., et al., Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med, 2001. 344(16): p. 1196-206.
- 25. Kurzawski, G., et al., Importance of microsatellite instability (MSI) in colorectal cancer: MSI as a diagnostic tool. Ann Oncol, 2004. 15 Suppl 4: p. iv283-4.
- 26. Halling, K.C., et al., Microsatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers. J Natl Cancer Inst, 1999. 91(15): p. 1295-303.
- 27. Kim, H., et al., Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol, 1994. 145(1): p. 148-56.
- 28. Thibodeau, S.N., et al., Microsatellite instability in colorectal cancer: different mutator phenotypes and the principal involvement of hMLH1. Cancer Res, 1998. 58(8): p. 1713-8.
- 29. Cunningham, J.M., et al., Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res, 1998. 58(15): p. 3455-60.
- 30. Kahlenberg, M.S., et al., Molecular prognostics in colorectal cancer. Surg Oncol, 2003. 12(3): p. 173-86.
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Articles |
| Authors | |
| Publication Date | December 31, 2019 |
| Submission Date | May 10, 2019 |
| Acceptance Date | August 15, 2019 |
| Published in Issue | Year 2019 Volume: 12 Issue: 3 |
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