Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Evaluation of MT1XT20 Single Quasi-Monomorphic Mononucleotide Marker for Characterizing Microsatellite Instability in Persian Lynch Syndrome Patients

  • Farahani, Najmeh (Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences) ;
  • Nikpour, Parvaneh (Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences) ;
  • Emami, Mohammad Hassan (Clinic of Gastrointestinal Diseases, Poursina Hakim Research Center, Isfahan University of Medical Sciences) ;
  • Hashemzadeh, Morteza (Cellular and Molecular Research Center, Shahrekord University of Medical Sciences) ;
  • Zeinalian, Mehrdad (Clinic of Gastrointestinal Diseases, Poursina Hakim Research Center, Isfahan University of Medical Sciences) ;
  • Shariatpanahi, Seyed Shervin (Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences) ;
  • Salehi, Rasoul (Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences)
  • Published : 2016.09.01
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Abstract

Background: Colorectal malignancies with high microsatellite instability (MSI-H), either hereditary (Lynch syndrome) or sporadic, demonstrate better prognosis and altered response to 5FU chemotherapy. It is now recommended to perform MSI testing for all new cases of colorectal cancer regardless of being categorized as hereditary or sporadic. For MSI detection, immunohistochemistry or PCR-based protocols using a cohort of various sets of STR markers are recommended. Here we aimed to evaluate a simplified protocol using just a single STR marker, MT1XT20 mononucleotide repeat, for detection of MSI in Lynch syndrome patients. A Promega five-marker MSI testing panel and immunohistochemistry (IHC) were used as the gold standard in conjunction with MT1XT20. Materials and Methods: Colorectal patients with a positive history of familial cancers were selected by evaluating medical records. Based on Amsterdam II criteria for Lynch syndrome 20 families were short listed. DNA was extracted from formalin fixed paraffin embedded tumour and adjacent normal tissues resected from the index case in each family. Extracted DNA was subjected to MT1XT20 mononucleotide marker analysis and assessment with a commercially available five marker MSI testing kit (Promega, USA). IHC also was performed on tissue sections and the results were compared with PCR based data. Results: Eight (40%), seven (35%) and five (25%) cases were MSI positive using with the Promega kit, IHC and MT1XT20, respectively. Among the markers included in Promega kit, BAT26 marker showed instability in all 8 samples. NR24 and NR21 markers showed instability in 7 (87.5%), and BAT25 and MONO 27 in 6 (75%) and 5 (62.5%). Conclusions: Although MT1XT20 was earlier reported as a valid standalone marker for MSI testing in CRC patients, we could not verify this in our Iranian patients. Instead BAT26 among the markers included in Promega MSI testing kit showed instability in all 8 MSI-H CRC samples. Therefore, it seems BAT26 could act well as a single marker for MSI testing in Iranian CRC patients.

Keywords

Acknowledgement

Supported by : Isfahan University of Medical Sciences

References

  1. Bacher JW, Flanagan LA, Smalley RL, et al (2004). Development of a fluorescent multiplex assay for detection of MSI-High tumors. Dis Markers, 20, 237-50. https://doi.org/10.1155/2004/136734
  2. Beamer LC, Grant ML, Espenschied CR, et al (2012). Reflex immunohistochemistry and microsatellite instability testing of colorectal tumors for Lynch syndrome among US cancer programs and follow-up of abnormal results. J Clin Oncol, 30, 1058-63. https://doi.org/10.1200/JCO.2011.38.4719
  3. Bianchi F, Galizia E, Catalani R, et al (2009). CAT25 is a mononucleotide marker to identify HNPCC patients. J Mol Diagn, 11, 248-52. https://doi.org/10.2353/jmoldx.2009.080155
  4. Boland CR (2013). The mystery of mismatch repair deficiency: lynch or lynch-like? Gastroenterol, 144, 868-70. https://doi.org/10.1053/j.gastro.2013.03.014
  5. Boland CR, Goel A (2010). Microsatellite instability in colorectal cancer. Gastroenterol, 138, 2073-87. https://doi.org/10.1053/j.gastro.2009.12.064
  6. 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, 5248-57.
  7. Bouzourene H, Taminelli L, Chaubert P, et al (2006). A costeffective algorithm for hereditary nonpolyposis colorectal cancer detection. Am J Clin Pathol, 125, 823-31. https://doi.org/10.1309/B0AFDT52ETMKEJBE
  8. Brennetot C, Buhard O, Jourdan F, et al (2005). Mononucleotide repeats BAT-26 and BAT-25 accurately detect MSI-H tumors and predict tumor content: implications for population screening. Int J Cancer, 113, 446-50. https://doi.org/10.1002/ijc.20586
  9. Buhard O, Cattaneo F, Wong YF, et al (2006). Multipopulation analysis of polymorphisms in five mononucleotide repeats used to determine the microsatellite instability status of human tumors. J Clin Oncol, 24, 241-51. https://doi.org/10.1200/JCO.2005.02.7227
  10. Chaksangchaichot P, Punyarit P, Petmitr S (2007). Novel hMSH2, hMSH6 and hMLH1 gene mutations and microsatellite instability in sporadic colorectal cancer. J Cancer Res Clin Oncol, 133, 65-70.
  11. Deschoolmeester V, Baay M, Wuyts W, et al (2008). Detection of microsatellite instability in colorectal cancer using an alternative multiplex assay of quasi-monomorphic mononucleotide markers. J Mol Diagn, 10, 154-9. https://doi.org/10.2353/jmoldx.2008.070087
  12. Esemuede I, Forslund A, Khan SA, et al (2010). Improved testing for microsatellite instability in colorectal cancer using a simplified 3-marker assay. Ann Surg Oncol, 17, 3370-8. https://doi.org/10.1245/s10434-010-1147-4
  13. Findeisen P, Kloor M, Merx S, et al (2005). T25 repeat in the 3' untranslated region of the CASP2 gene: a sensitive and specific marker for microsatellite instability in colorectal cancer. Cancer Res, 65, 8072-8. https://doi.org/10.1158/0008-5472.CAN-04-4146
  14. Fishel R (1999). Signaling mismatch repair in cancer. Nat Med, 5, 1239-41. https://doi.org/10.1038/15191
  15. Fukutomi Y, Moriwaki H, Nagase S, et al (2002). Metachronous colon tumors: risk factors and rationale for the surveillance colonoscopy after initial polypectomy. J Cancer Res Clin Oncol, 128, 569-74. https://doi.org/10.1007/s00432-002-0375-9
  16. Haghighi MM, Javadi GR, Parivar K, et al (2010). Frequent MSI mononucleotide markers for diagnosis of hereditary nonpolyposis colorectal cancer. Asian Pac J Cancer Prev, 11, 1033-5.
  17. Haghighi MM, Vahedi M, Mohebbi SR, et al (2009). Comparison of survival between patients with hereditary non polyposis colorectal cancer (HNPCC) and sporadic colorectal cancer. Asian Pac J Cancer Prev, 10, 209-12.
  18. Ichikawa A, Sugano K, Fujita S (2001). DNA variants of BAT-25 in Japanese, a locus frequently used for analysis of microsatellite instability. Jpn J Clin Oncol, 31, 346-8. https://doi.org/10.1093/jjco/hye066
  19. Ionov Y, Peinado MA, Malkhosyan S, et al (1993). Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature, 363, 558-61. https://doi.org/10.1038/363558a0
  20. Lindor NM, Burgart LJ, Leontovich O, et al (2002). Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol, 20, 1043-8. https://doi.org/10.1200/JCO.2002.20.4.1043
  21. Lynch HT, Boland CR, Gong G, et al (2006). Phenotypic and genotypic heterogeneity in the Lynch syndrome: diagnostic, surveillance and management implications. Eur J Hum Genet, 14, 390-402. https://doi.org/10.1038/sj.ejhg.5201584
  22. Lynch HT, de la Chapelle A (2003). Hereditary colorectal cancer. N Engl J Med, 348, 919-32. https://doi.org/10.1056/NEJMra012242
  23. Nemati A, Rahmatabadi ZK, Fatemi A, et al (2012). Hereditary nonpolyposis colorectal cancer and familial colorectal cancer in Central part of Iran, Isfahan. J Res Med Sci, 17, 67-73.
  24. Patil DT, Bronner MP, Portier BP, et al (2012). A five-marker panel in a multiplex PCR accurately detects microsatellite instability-high colorectal tumors without control DNA. Diagn Mol Pathol, 21, 127-33. https://doi.org/10.1097/PDM.0b013e3182461cc3
  25. Ribic CM, Sargent DJ, Moore MJ, et al (2003). Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med, 349, 247-57. https://doi.org/10.1056/NEJMoa022289
  26. Rodriguez-Bigas M, Moeslein G (2013). Surgical treatment of hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome). Fam Cancer, 12, 295-300. https://doi.org/10.1007/s10689-013-9626-y
  27. Shemirani AI, Haghighi MM, Zadeh SM, et al (2011). Simplified MSI marker panel for diagnosis of colorectal cancer. Asian Pac J Cancer Prev, 12, 2101-4.
  28. Shia J (2008). Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. The utility of immunohistochemistry. J Mol Diagn, 10, 293-300. https://doi.org/10.2353/jmoldx.2008.080031
  29. Tautz D (1989). Hypervariability of simple sequences as a general source for polymorphic DNA markers. Nucleic Acids Res, 17, 6463-71. https://doi.org/10.1093/nar/17.16.6463
  30. Tejpar S, Saridaki Z, Delorenzi M, et al (2011). Microsatellite instability, prognosis and drug sensitivity of stage II and III colorectal cancer: more complexity to the puzzle. J Natl Cancer Inst, 103, 841-4. https://doi.org/10.1093/jnci/djr170
  31. Thibodeau SN, French AJ, Roche PC, et al (1996). Altered expression of hMSH2 and hMLH1 in tumors with microsatellite instability and genetic alterations in mismatch repair genes. Cancer Res, 56, 4836-40.
  32. Vatandoost N, Ghanbari J, Mojaver M, et al (2016). Early detection of colorectal cancer: from conventional methods to novel biomarkers. J Cancer Res Clin Oncol, 142, 341-51. https://doi.org/10.1007/s00432-015-1928-z
  33. Ward R, Meldrum C, Williams R, et al (2002). Impact of microsatellite testing and mismatch repair protein expression on the clinical interpretation of genetic testing in hereditary non-polyposis colorectal cancer. J Cancer Res Clin Oncol, 128, 403-11. https://doi.org/10.1007/s00432-002-0361-2
  34. Xicola RM, Llor X, Pons E, et al (2007). Performance of different microsatellite marker panels for detection of mismatch repair-deficient colorectal tumors. J Natl Cancer Inst, 99, 244-52. https://doi.org/10.1093/jnci/djk033
  35. Zeinalian M, Emami M, Salehi R, et al (2015a). Molecular analysis of Iranian colorectal cancer patients at risk for Lynch syndrome: a new molecular, clinicopathological feature. J Gastrointest Cancer, 46, 118-25. https://doi.org/10.1007/s12029-015-9696-1
  36. Zeinalian M, Emami MH, Naimi A, et al (2015b). Immunohistochemical analysis of mismatch repair proteins in Iranian colorectal cancer patients at risk for lynch syndrome. Iran J Cancer Prev, 8, 11-7.