DOI QR코드

DOI QR Code

Colorectal Carcinoma in Malaysians: DNA Mismatch Repair Pattern in a Multiethnic Population

  • Cheah, Phaik-Leng (Department of Pathology, Faculty of Medicine, University of Malaya) ;
  • Looi, Lai-Meng (Department of Pathology, Faculty of Medicine, University of Malaya) ;
  • Teoh, Kean-Hooi (Department of Pathology, Faculty of Medicine, University of Malaya) ;
  • Rahman, Nazarina Abdul (Department of Pathology, Faculty of Medicine, University of Malaya) ;
  • Wong, Li-Xuan (Department of Pathology, Faculty of Medicine, University of Malaya) ;
  • Tan, Soo-Yong (Department of Pathology, Faculty of Medicine, University of Malaya)
  • Published : 2014.04.01

Abstract

Background: The interesting preponderance of Chinese with colorectal carcinoma (CRC) amongst the three major ethnic groups in Malaysia prompted a study to determine DNA mismatch repair (MMR) status in our CRC and attempt correlation with patient age, gender and ethnicity as well as location, grade, histological type and stage of tumour. Histologically re-confirmed CRC, diagnosed between $1^{st} $January 2005 and $31^{st}$ December 2007 at the Department of Pathology, University of Malaya Medical Centre, were immunohistochemically stained with monoclonal antibodies to MMR proteins, MLH1, MSH2, MSH6 and PMS2 on the Ventana Benchmark XT autostainer. Of the 142 CRC cases entered into the study, there were 82 males and 60 females (M:F=1.4:1). Ethnically, 81 (57.0%) were Chinese, 32 (22.5%) Malays and 29 (20.4%) Indians. The patient ages ranged between 15-87 years (mean=62.4 years) with 21 cases <50-years and 121 ${\geq}50$-years of age. 14 (9.9%) CRC showed deficient MMR (dMMR). Concurrent loss of MLH1 and PMS2 occurred in 10, MSH2 and MSH6 in 2 with isolated loss of MSH6 in 1 and PMS2 in 1. dMMR was noted less frequently amongst the Chinese (6.2%) in comparison with their combined Malay and Indian counterparts (14.8%), and was associated with right sided and poorly differentiated tumours (p<0.05). 3 of the 5 (60.0%) dMMR CRC cases amongst the Chinese and 1 of 9 cases (11.1%) amongst the combined Malay and Indian group were <50-years of age. No significant association of dMMR was noted with patient age and gender, tumour stage or mucinous type.

Keywords

References

  1. Aaltonen LA, Peltomaki P, Leach FS, et al (1993). Clues to the pathogenesis of familial colorectal cancer. Science, 260, 812-6. https://doi.org/10.1126/science.8484121
  2. Al-Naggar RA, Bobryshev YV (2013). Knowledge of colorectal cancer screening among young Malaysians. Asian Pac J Cancer Prev, 14, 1969-74. https://doi.org/10.7314/APJCP.2013.14.3.1969
  3. Ashktorab H, Smoot DT, Carethers JM, et al (2003). High incidence of microsatellite instability in colorectal cancer from African Americans. Clin Cancer Res, 9, 1112-7.
  4. Blenkinsopp WK, Stewart-Brown S, Blesovsky L, Kearney G, Fielding LP (1981). Histopathology reporting in large bowel cancer. J Clin Pathol, 34, 509-13. https://doi.org/10.1136/jcp.34.5.509
  5. Chan TL, Yuen ST, Chung LP, et al (1999). Frequent microsatellite instability and mismatch repair gene mutations in young Chinese patients with colorectal cancer. J Natl Cancer Inst, 91, 1221-6. https://doi.org/10.1093/jnci/91.14.1221
  6. De Jesus-Monge WE, Gonzalez-Keelan C, Zhao R, et al (2010). Mismatch repair protein expression and colorectal cancer in hispanics from puerto rico. Fam Cancer, 9, 155-66. https://doi.org/10.1007/s10689-009-9310-4
  7. Fearon ER (2011). Molecular genetics of colorectal cancer. Annu Rev Pathol, 6, 479-507. https://doi.org/10.1146/annurev-pathol-011110-130235
  8. Hearne CM, Ghosh S, Todd JA (1992). Microsatellites for linkage analysis of genetic traits. Trends Genet, 8, 288-94. https://doi.org/10.1016/0168-9525(92)90256-4
  9. Hoogerbrugge N, Willems R, Van Krieken HJ, et al (2003). Very low incidence of microsatellite instability in rectal cancers from families at risk for HNPCC. Clin Genet, 63, 64-70.
  10. Iacopetta B, Grieu F, Amanuel B (2010). Microsatellite instability in colorectal cancer. Asian Pac J Clin Oncol, 6, 260-9. https://doi.org/10.1111/j.1743-7563.2010.01335.x
  11. Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M (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
  12. Jin HY, Liu X, Li VK, et al (2008). Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer. BMC Cancer, 8, 44. https://doi.org/10.1186/1471-2407-8-44
  13. Kanthan R, Senger JL, Kanthan SC (2012). Molecular events in primary and metastatic colorectal carcinoma: a review. Patholog Res Int, 2012, 597497.
  14. Koopman M, Kortman GA, Mekenkamp L, et al (2009). Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer, 100, 266-73. https://doi.org/10.1038/sj.bjc.6604867
  15. Legolvan MP, Taliano RJ, Resnick MB (2012). Application of molecular techniques in the diagnosis, prognosis and management of patients with colorectal cancer: a practical approach. Hum Pathol, 43, 1157-68. https://doi.org/10.1016/j.humpath.2012.03.003
  16. Lim KG, Ganesanathan S, Palaiyan K, et al (2008). Cancer incidence in peninsular Malaysia 2003-2005. The third report of the national cancer registry. Kuala Lumpur: national cancer registry. Ministry of Health Malaysia, 83-6.
  17. Loh KW, Majid HA, Dahlui M, Roslani AC, Su TT (2013). Sociodemographic predictors of recall and recognition of colorectal cancer symptoms and anticipated delay in help-seeking in a multiethnic Asian population. Asian Pac J Cancer Prev, 14, 3799-804. https://doi.org/10.7314/APJCP.2013.14.6.3799
  18. Mojtahed A, Schrijver I, Ford JM, Longacre TA, Pai RK (2011). A two-antibody mismatch repair protein immunohistochemistry screening approach for colorectal carcinomas, skin sebaceous tumors, and gynecologic tract carcinomas. Mod Pathol, 24, 1004-14. https://doi.org/10.1038/modpathol.2011.55
  19. Niessen RC, Berends MJ, Wu Y, et al (2006). Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer. Gut, 55, 1781-8. https://doi.org/10.1136/gut.2005.090159
  20. Parsons R, Li GM, Longley MJ, et al (1993). Hypermutability and mismatch repair deficiency in RER+tumor cells. Cell, 75, 1227-36. https://doi.org/10.1016/0092-8674(93)90331-J
  21. Pinol V, Castells A, Andreu M (2005). Gastrointestinal Oncology Group of the Spanish Gastroenterological Association. Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA, 293, 1986-94. https://doi.org/10.1001/jama.293.16.1986
  22. Population and Housing Census, Malaysia (2010). Department of statistics Malaysia official website http://www.statistics.gov.my
  23. Shia J, Tang LH, Vakiani E, et al (2009). Immunohistochemistry as first-line screening for detecting colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome: a 2-antibody panel may be as predictive as a 4-antibody panel. Am J Surg Pathol, 33, 1639-45. https://doi.org/10.1097/PAS.0b013e3181b15aa2
  24. Sinicrope FA, Sargent DJ (2012). Molecular pathways: microsatellite instability in colorectal cancer: prognostic, predictive, and therapeutic implications. Clin Cancer Res, 18, 1506-12. https://doi.org/10.1158/1078-0432.CCR-11-1469
  25. Sobin L, Gospodarowicz M, Wittekind C (2009). eds. TNM Classification of malignant tumors. 7th ed. Hoboken, NJ: John Wiley & Sons, Inc,
  26. Sylvester BE, Huo D, Khramtsov A, et al (2012). Molecular analysis of colorectal tumors within a diverse patient cohort at a single institution. Clin Cancer Res, 18, 350-9. https://doi.org/10.1158/1078-0432.CCR-11-1397
  27. Tan LP, Ng BK, Balraj P, Lim PK, Peh SC (2007). No difference in the occurrence of mismatch repair defects and APC and CTNNB1 genes mutation in a multi-racial colorectal carcinoma patient cohort. Pathology, 39, 228-34. https://doi.org/10.1080/00313020701230757
  28. Thibodeau SN, Bren G, Schaid D (1993). Microsatellite instability in cancer of the proximal colon. Science, 260, 816-9. https://doi.org/10.1126/science.8484122
  29. Truninger K, Menigatti M, Luz J, et al (2005). Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer. Gastroenterol, 128, 1160-71. https://doi.org/10.1053/j.gastro.2005.01.056
  30. Umar A, Boland CR, Terdiman JP, et al (2004). Revised bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst, 96, 261-8. https://doi.org/10.1093/jnci/djh034
  31. Vilkin A, Niv Y, Nagasaka T, Morgenstern S, et al (2009). Microsatellite instability, MLH1 promoter methylation, and BRAF mutation analysis in sporadic colorectal cancers of different ethnic groups in Israel. Cancer, 115, 760-9. https://doi.org/10.1002/cncr.24019
  32. 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, 388-96.
  33. Yearsley M, Hampel H, Lehman A, et al (2006). Histologic features distinguish microsatellite-high from microsatellite-low and microsatellite-stable colorectal carcinomas, but do not differentiate germline mutations from methylation of the MLH1 promoter. Hum Pathol, 37, 831-8. https://doi.org/10.1016/j.humpath.2006.02.009
  34. Yusoff HM, Daud N, Noor NM, Rahim AA (2013). Participation and barriers to colorectal cancer screening in Malaysia. Asian Pac J Cancer Prev, 14, 3799-804. https://doi.org/10.7314/APJCP.2013.14.6.3799

Cited by

  1. Chemopreventive Efficacy of Andrographis paniculata on Azoxymethane-Induced Aberrant Colon Crypt Foci In Vivo vol.9, pp.11, 2014, https://doi.org/10.1371/journal.pone.0111118
  2. Analysis of Hereditary Nonpolyposis Colorectal Cancer in Malay Cohorts using Immunohistochemical Screening vol.16, pp.9, 2015, https://doi.org/10.7314/APJCP.2015.16.9.3767