High Frequency of Microsatellite Instability among Non-Metastatic Gastric Cancer
,
Abstract
Background: Microsatellite instability (MSI) is considered a key factor in carcinogenesis and a genetic alteration pattern in many types of cancers such as gastric cancer (GC). Although the role of MSI in colorectal cancer (CRC) is well known, its prognostic impact on GC has not been clearly defined. The assessment of MSI in GC has not been documented in the Iranian population yet. Therefore, this study analyzed the association of MSI status with GC in Iranian patients.
Materials and Methods: We compared the frequency of MSI at 5 loci from formalin-fixed paraffin-embedded (FFPE) gastrectomy specimens, between metastatic and non-metastatic cases of GC (N = 60). A panel of five quasi-monomorphic markers and a single dinucleotide marker with linker-based fluorescent primers was used.
Results: MSI was observed in 46.6% of cases, including MSI-high (H) (33.3%) and MSI-Low (L) (13.3%). Moreover, the most unstable and stable markers in our study were NR-21 and BAT-26 accordingly. MSI-H and MSI were seen more frequently in non-metastatic tumors (p= 0.028 and p= 0.019, respectively).
Conclusion: The current study showed MSI status more frequently in non-metastatic GC which may reflect a good prognostic factor in GC like CRC. Although, larger and more comprehensive studies are needed to confirm this statement. A panel consisting of NR-21, BAT-25, and NR-27 mononucleotide markers appears to be reliable and useful markers for detecting MSI in GC in Iranian patients.
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8. Salipante SJ, Scroggins SM, Hampel HL, et al. Microsatellite instability detection by next generation sequencing. Clin Chem. 2014;60(9):1192-9.
9. Haraldsdottir S. Microsatellite instability testing using next-generation sequencing data and therapy implications. JCO Precis Oncol. 2017;1:1-4.
10. Huang Yq, Yuan Y, Ge Wt, et al. Comparative features of colorectal and gastric cancers with microsatellite instability in Chinese patients. J Zhejiang Univ Sci B. 2010;11(9):647-53.
11. Zhao H, Thienpont B, Yesilyurt BT, et al. Mismatch repair deficiency endows tumors with a unique mutation signature and sensitivity to DNA double-strand breaks. Elife. 2014;3:e02725.
12. Wu S, Liu X, Wang J, et al. DNA Mismatch Repair Deficiency Detection in Colorectal Cancer by a New Microsatellite Instability Analysis System. Interdiscip Sci. 2020;12(2):145-154.
13. Sayyed-Hosseinian SH, Hassankhani GG, Bagheri F, et al. Validation of the Persian version of the American orthopedic foot and ankle Society score (AOFAS) questionnaire. Arch Bone Jt Surg. 2018;6(3):233-239.
14. Bae YS, Kim H, Noh SH, et al. Usefulness of immunohistochemistry for microsatellite instability screening in gastric cancer. Gut Liver. 2015;9(5):629-35.
15. Yuza K, Nagahashi M, Watanabe S, et al. Hypermutation and microsatellite instability in gastrointestinal cancers. Oncotarget. 2017;8(67):112103- 112115.
16. Bacher JW, Clipson L , Steffen LS, et al. Microsatellite Instability and its Significance to Hereditary and Sporadic Cancer. . 2016. In: Microsatellite Markers [Internet]. London: IntechOpen.
17. Pagin A, Zerimech F, Leclerc J, et al. Evaluation of a new panel of six mononucleotide repeat markers for the detection of DNA mismatch repair-deficient tumours. Br J Cancer. 2013; 108(10): 2079–2087.
18. Zhu L, Li Z, Wang Y, et al. Microsatellite instability and survival in gastric cancer: A systematic review and meta‑analysis. Mol Clin Oncol. 2015;3(3):699-705.
19. Shi C, Berlin J, Branton P, et al. Protocol for the examination of specimens from patients with carcinoma of the esophagus. Cancer Protocol Templates Northfield, IL: College of American Pathologists. 2017.
20. Moradian F, Fararouei M, Karami M, et al. Trend of geographical distribution
of stomach cancer in Iran from 2004 to 2014. BMC Gastroenterol. 2022;22(4).
21. Wong YF, Cheung TH, Lo KWK, et al. Detection of microsatellite instability in endometrial cancer: advantages of a panel of five mononucleotide repeats over the National Cancer Institute panel of markers. Carcinogenesis. 2006;27(5):951-5.
22. Xicola RM, Llor X, Pons E, et al. Performance of different microsatellite marker panels for detection of mismatch repair–deficient colorectal tumors. J Natl Cancer Inst. 2007 Feb 7;99(3):244-52.
23. Mukherjee M, Vaish M, Mittal R, et al. Allelic variation of BAT-26 and BAT-40 poly-adenine repeat loci in North Indians. Int J Mol Med. 2002;9(1):91-4.
24. Buhard O, Suraweera N, Lectard A, et al. Quasimonomorphic mononucleotide repeats for high-level microsatellite instability analysis. Dis Markers. 2004;20(4-5):251-7.
25. Buhard O, Cattaneo F, Wong YF, et al. Multipopulation analysis of polymorphisms in five mononucleotide repeats used to determine the microsatellite instability status of human tumors. J Clin Oncol. 2006;24(2):241-51.
26. Esmailnia G, Montazer-Haghighi M, Javadi G, et al. Microsatellite instability markers status in colorectal cancer. Zahedan J Res Med Sci. 2013;16(12):26-30.
27. Shemirani AI, Haghighi MM, Zadeh SM, et al. Simplified MSI marker panel for diagnosis of colorectal cancer. Asian Pac J Cancer Prev. 2011;12(8):2101-4.
28. Farahani N, Nikpour P, Emami MH, et al. Evaluation of MT1XT20 single quasi-monomorphic mononucleotide marker for characterizing microsatellite instability in persian lynch syndrome patients. Asian Pac J Cancer Prev. 2016;17(9):4259-4265.
29. Campanella NC, Berardinelli GN, Scapulatempo-Neto C, et al. Optimization of a pentaplex panel for MSI analysis without control DNA in a Brazilian population: correlation with ancestry markers. Eur J Hum Genet. 2014;22(7):875-80.
30. Kunitomi H, Banno K, Yanokura M, et al. New use of microsatellite instability analysis in endometrial cancer. Oncol Lett. 2017;14(3):3297-3301.
31. Karpińska K, Lewandowska M, Urasińska E. Genetic and histological subtypes of gastric cancer reviewed, particularly emphasising on microsatellite instability and E-cadherin gene mutation. Nowotwory J Oncol. 2017;67(3):193-200.
32. Park J, Yoo HM, Jang W, et al. Distribution of somatic mutations of cancer-related genes according to microsatellite instability status in Korean gastric cancer. Medicine. 2017;96(25).
33. Xing L, Guo H, Zheng D, et al. Gastric cancer is associated with a high rate of microsatellite instability versus chronic gastritis: A retrospective study. Revista Romana de Medicina de Laborator. 2020;28(1):57-65.
34. Li K, Luo H, Huang L, et al. Microsatellite instability: a review of what the oncologist should know. Cancer Cell Int. 2020;20(1):16.
35. Strand MS, Lockhart AC, Fields RC. Genetics of gastric cancer. Surg Clin North Am. 2017;97(2):345-370
36. Leung WK, Kim JJ, Kim JG, et al. Microsatellite instability in gastric intestinal metaplasia in patients with and without gastric cancer. Am J Pathol. 2000 ;156(2):537-43
37. Polom K, Marrelli D, Roviello G, et al. Molecular key to understand the gastric cancer biology in elderly patients—the role of microsatellite instability. J Surg Oncol. 2017;115(3):344-350.
38. Nakashima H, Honda M, Inoue H, et al. Microsatellite instability in multiple gastric cancers. Int J cancer. 1995;64(4):239-42.
39. Yang G, Zheng Ry, Jin Zs. Correlations between microsatellite instability and the biological behaviour of tumours. J Cancer Res Clin Oncol. 2019;145(12):2891-2899.
40- Cui M, Li P, Mao Y, et al.
Implication of Microsatellite Instability in Chinese
Cohort of Human Cancers. Cancer Manag Res. 2020;12:10287-10295.
2. Li X, Wu WK, Xing R, et al. Distinct subtypes of gastric cancer defined by molecular characterization include novel mutational signatures with prognostic capability. Cancer Res. 2016;76(7):1724-32
3. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202-9.
4. Cui M, Li P, Mao Y, et al. Implication of Microsatellite Instability in Chinese Cohort of Human Cancers. Cancer Manag Res. 2020;12:10287-10295.
5. Suraweera N, Duval A, Reperant M, et al. Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology. 2002;123(6):1804-11.
6. Kim JY, Shin NR, Kim A, et al. Microsatellite instability status in gastric cancer: a reappraisal of its clinical significance and relationship with mucin phenotypes. Korean J Pathol. 2013;47(1):28-35.
7. Gan C, Love C, Beshay V, et al. Applicability of next generation sequencing technology in microsatellite instability testing. Genes(Basel). 2015;6(1):46-59.
8. Salipante SJ, Scroggins SM, Hampel HL, et al. Microsatellite instability detection by next generation sequencing. Clin Chem. 2014;60(9):1192-9.
9. Haraldsdottir S. Microsatellite instability testing using next-generation sequencing data and therapy implications. JCO Precis Oncol. 2017;1:1-4.
10. Huang Yq, Yuan Y, Ge Wt, et al. Comparative features of colorectal and gastric cancers with microsatellite instability in Chinese patients. J Zhejiang Univ Sci B. 2010;11(9):647-53.
11. Zhao H, Thienpont B, Yesilyurt BT, et al. Mismatch repair deficiency endows tumors with a unique mutation signature and sensitivity to DNA double-strand breaks. Elife. 2014;3:e02725.
12. Wu S, Liu X, Wang J, et al. DNA Mismatch Repair Deficiency Detection in Colorectal Cancer by a New Microsatellite Instability Analysis System. Interdiscip Sci. 2020;12(2):145-154.
13. Sayyed-Hosseinian SH, Hassankhani GG, Bagheri F, et al. Validation of the Persian version of the American orthopedic foot and ankle Society score (AOFAS) questionnaire. Arch Bone Jt Surg. 2018;6(3):233-239.
14. Bae YS, Kim H, Noh SH, et al. Usefulness of immunohistochemistry for microsatellite instability screening in gastric cancer. Gut Liver. 2015;9(5):629-35.
15. Yuza K, Nagahashi M, Watanabe S, et al. Hypermutation and microsatellite instability in gastrointestinal cancers. Oncotarget. 2017;8(67):112103- 112115.
16. Bacher JW, Clipson L , Steffen LS, et al. Microsatellite Instability and its Significance to Hereditary and Sporadic Cancer. . 2016. In: Microsatellite Markers [Internet]. London: IntechOpen.
17. Pagin A, Zerimech F, Leclerc J, et al. Evaluation of a new panel of six mononucleotide repeat markers for the detection of DNA mismatch repair-deficient tumours. Br J Cancer. 2013; 108(10): 2079–2087.
18. Zhu L, Li Z, Wang Y, et al. Microsatellite instability and survival in gastric cancer: A systematic review and meta‑analysis. Mol Clin Oncol. 2015;3(3):699-705.
19. Shi C, Berlin J, Branton P, et al. Protocol for the examination of specimens from patients with carcinoma of the esophagus. Cancer Protocol Templates Northfield, IL: College of American Pathologists. 2017.
20. Moradian F, Fararouei M, Karami M, et al. Trend of geographical distribution
of stomach cancer in Iran from 2004 to 2014. BMC Gastroenterol. 2022;22(4).
21. Wong YF, Cheung TH, Lo KWK, et al. Detection of microsatellite instability in endometrial cancer: advantages of a panel of five mononucleotide repeats over the National Cancer Institute panel of markers. Carcinogenesis. 2006;27(5):951-5.
22. Xicola RM, Llor X, Pons E, et al. Performance of different microsatellite marker panels for detection of mismatch repair–deficient colorectal tumors. J Natl Cancer Inst. 2007 Feb 7;99(3):244-52.
23. Mukherjee M, Vaish M, Mittal R, et al. Allelic variation of BAT-26 and BAT-40 poly-adenine repeat loci in North Indians. Int J Mol Med. 2002;9(1):91-4.
24. Buhard O, Suraweera N, Lectard A, et al. Quasimonomorphic mononucleotide repeats for high-level microsatellite instability analysis. Dis Markers. 2004;20(4-5):251-7.
25. Buhard O, Cattaneo F, Wong YF, et al. Multipopulation analysis of polymorphisms in five mononucleotide repeats used to determine the microsatellite instability status of human tumors. J Clin Oncol. 2006;24(2):241-51.
26. Esmailnia G, Montazer-Haghighi M, Javadi G, et al. Microsatellite instability markers status in colorectal cancer. Zahedan J Res Med Sci. 2013;16(12):26-30.
27. Shemirani AI, Haghighi MM, Zadeh SM, et al. Simplified MSI marker panel for diagnosis of colorectal cancer. Asian Pac J Cancer Prev. 2011;12(8):2101-4.
28. Farahani N, Nikpour P, Emami MH, et al. Evaluation of MT1XT20 single quasi-monomorphic mononucleotide marker for characterizing microsatellite instability in persian lynch syndrome patients. Asian Pac J Cancer Prev. 2016;17(9):4259-4265.
29. Campanella NC, Berardinelli GN, Scapulatempo-Neto C, et al. Optimization of a pentaplex panel for MSI analysis without control DNA in a Brazilian population: correlation with ancestry markers. Eur J Hum Genet. 2014;22(7):875-80.
30. Kunitomi H, Banno K, Yanokura M, et al. New use of microsatellite instability analysis in endometrial cancer. Oncol Lett. 2017;14(3):3297-3301.
31. Karpińska K, Lewandowska M, Urasińska E. Genetic and histological subtypes of gastric cancer reviewed, particularly emphasising on microsatellite instability and E-cadherin gene mutation. Nowotwory J Oncol. 2017;67(3):193-200.
32. Park J, Yoo HM, Jang W, et al. Distribution of somatic mutations of cancer-related genes according to microsatellite instability status in Korean gastric cancer. Medicine. 2017;96(25).
33. Xing L, Guo H, Zheng D, et al. Gastric cancer is associated with a high rate of microsatellite instability versus chronic gastritis: A retrospective study. Revista Romana de Medicina de Laborator. 2020;28(1):57-65.
34. Li K, Luo H, Huang L, et al. Microsatellite instability: a review of what the oncologist should know. Cancer Cell Int. 2020;20(1):16.
35. Strand MS, Lockhart AC, Fields RC. Genetics of gastric cancer. Surg Clin North Am. 2017;97(2):345-370
36. Leung WK, Kim JJ, Kim JG, et al. Microsatellite instability in gastric intestinal metaplasia in patients with and without gastric cancer. Am J Pathol. 2000 ;156(2):537-43
37. Polom K, Marrelli D, Roviello G, et al. Molecular key to understand the gastric cancer biology in elderly patients—the role of microsatellite instability. J Surg Oncol. 2017;115(3):344-350.
38. Nakashima H, Honda M, Inoue H, et al. Microsatellite instability in multiple gastric cancers. Int J cancer. 1995;64(4):239-42.
39. Yang G, Zheng Ry, Jin Zs. Correlations between microsatellite instability and the biological behaviour of tumours. J Cancer Res Clin Oncol. 2019;145(12):2891-2899.
40- Cui M, Li P, Mao Y, et al.
Implication of Microsatellite Instability in Chinese
Cohort of Human Cancers. Cancer Manag Res. 2020;12:10287-10295.
| Files | ||
| Issue | Vol 16, No 4 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v16i4.10882 | |
| Keywords | ||
| Gastric cancer; Microsatellite instability; Metastatic; Fragment analysis | ||
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How to Cite
1.
Fanaei K, Salahshourifar I, Ameli F, Esfandbod M, Irani S. High Frequency of Microsatellite Instability among Non-Metastatic Gastric Cancer. Int J Hematol Oncol Stem Cell Res. 2022;16(4):239-249.
