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Mismatch repair protein expression and colorectal cancer in Hispanics from Puerto Rico

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Abstract

Colorectal cancer (CRC) is a leading cause of morbidity and mortality and alterations in mismatch repair (MMR) genes, leading to absent protein (negative) expression, are responsible for approximately 20% of CRC cases. Immunohistochemistry is a tool for prescreening of MMR protein expression in CRC but the literature on its use on Hispanics is scarce. However, Hispanics represent the second leading ethnicity in the United States (US) and CRC is a public health burden in this group. Our objectives were to determine the frequency of MMR protein-negative CRC and to evaluate its association with clinical and pathological characteristics among Hispanics from Puerto Rico, for the first time to our knowledge. A retrospective observational study of unselected CRC patients from the Puerto Rico Medical Center from 2001 to 2005 was done. MLH1 and MSH2, the most commonly altered MMR genes, protein expression was evaluated using immunohistochemistry, with microsatellite instability (MSI) and BRAF gene analyses in the absence of MLH1 protein expression. One-hundred sixty-four CRC patients were evaluated: the overall MMR protein-negative frequency was 4.3%, with 0.6% frequency of co-occurrence of MLH1-protein negative expression, MSI-high, and normal BRAF gene. MMR protein-negative expression was associated with proximal colon location (P = 0.02) and poor histological tumor differentiation (P = 0.001), but not with other characteristics. The frequency of MMR protein-negative CRC in Hispanics from Puerto Rico was lower than reported in other populations. This finding may explain the lower CRC incidence rate among US Hispanics as compared to US non-Hispanic whites and blacks.

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Abbreviations

CIMP:

CpG island methylation phenotype

CRC:

Colorectal cancer

HNPCC:

Hereditary nonpolyposis colorectal cancer

HOIGM:

Hospital Oncologico Isaac Gonzalez-Martinez

MMR:

Mismatch repair

MSI:

Microsatellite instability

MSI-H:

Microsatellite instability-high

PCR:

Polymerase chain reaction

PRMC:

Puerto Rico Medical Center

US:

United States

References

  1. Colorectal cancer (2003) In: Steward BW, Kleihues P (ed) World cancer report. IARC Press, Lyon

  2. Jemal A, Siegel R, Ward E et al (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249

    Article  PubMed  Google Scholar 

  3. Raut CP, Pawlik TM, Rodriguez-Bigas MA (2004) Clinicopathologic features in colorectal cancer patients with microsatellite instability. Mutat Res 568:275–282

    CAS  PubMed  Google Scholar 

  4. Soreide K, Janssen EA, Soiland H et al (2006) Microsatellite instability in colorectal cancer. Br J Surg 93:395–406

    Article  CAS  PubMed  Google Scholar 

  5. Wu J, Gu L, Wang H et al (1999) Mismatch repair processing of carcinogen-DNA adducts triggers apoptosis. Mol Cell Biol 19:8292–8301

    CAS  PubMed  Google Scholar 

  6. Hickman MJ, Samson LD (1999) Role of DNA mismatch repair and p53 in signaling induction of apoptosis by alkylating agents. Proc Natl Acad Sci USA 96:10764–10769

    Article  CAS  PubMed  Google Scholar 

  7. Koessler T, Azzato EM, Perkins B et al (2009) Common germline variation in mismatch repair genes and survival after a diagnosis of colorectal cancer. Int J Cancer 124:1887–1891

    Article  CAS  PubMed  Google Scholar 

  8. Wijnen JT, Brohet RM, van Eijk R et al (2009) Chromosome 8q23.3 and 11q23.1 variants modify colorectal cancer risk in Lynch syndrome. Gastroenterology 136:131–137

    Article  PubMed  Google Scholar 

  9. Lynch HT, Smyrk T (1996) Hereditary nonpolyposis colorectal cancer (Lynch syndrome). An updated review. Cancer 78:1149–1167

    Article  CAS  PubMed  Google Scholar 

  10. Boland CR, Koi M, Chang DK et al (2008) The biochemical basis of microsatellite instability and abnormal immunohistochemistry and clinical behavior in Lynch syndrome: from bench to bedside. Fam Cancer 7:41–52

    Article  CAS  PubMed  Google Scholar 

  11. Raevaara TE, Korhonen MK, Lohi H et al (2005) Functional significance and clinical phenotype of nontruncating mismatch repair variants of MLH1. Gastroenterology 129:537–549

    CAS  PubMed  Google Scholar 

  12. Hampel H, Stephens JA, Pukkala E et al (2005) Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset. Gastroenterology 129:415–421

    PubMed  Google Scholar 

  13. Shin YK, Heo SC, Shin JH et al (2004) Germline mutations in MLH1, MSH2 and MSH6 in Korean hereditary non-polyposis colorectal cancer families. Hum Mutat 24:351

    Article  PubMed  CAS  Google Scholar 

  14. Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives (2009) Genet Med 11:35–41

  15. Lynch HT, Boland CR, Rodriguez-Bigas MA et al (2007) Who should be sent for genetic testing in hereditary colorectal cancer syndromes? J Clin Oncol 25:3534–3542

    Article  PubMed  Google Scholar 

  16. 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

    Article  CAS  PubMed  Google Scholar 

  17. Ricciardiello L, Boland CR (2005) Lynch syndrome (hereditary non-polyposis colorectal cancer): current concepts and approaches to management. Curr Gastroenterol Rep 7:412–420

    Article  PubMed  Google Scholar 

  18. De Jong AE, Morreau H, Van Puijenbroek M et al (2004) The role of mismatch repair gene defects in the development of adenomas in patients with HNPCC. Gastroenterology 126:42–48

    Article  PubMed  CAS  Google Scholar 

  19. Soreide K (2007) Molecular testing for microsatellite instability and DNA mismatch repair defects in hereditary and sporadic colorectal cancers—ready for prime time? Tumour Biol 28:290–300

    Article  PubMed  CAS  Google Scholar 

  20. Chung DC, Rustgi AK (2003) The hereditary nonpolyposis colorectal cancer syndrome: genetics and clinical implications. Ann Intern Med 138:560–570

    CAS  PubMed  Google Scholar 

  21. Rouleau E, Lefol C, Bourdon V et al (2009) Quantitative PCR high-resolution melting (qPCR-HRM) curve analysis, a new approach to simultaneously screen point mutations and large rearrangements: application to MLH1 germline mutations in Lynch syndrome. Hum Mutat 30:867–875

    Article  CAS  PubMed  Google Scholar 

  22. Lindor NM, Burgart LJ, Leontovich O et al (2002) Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol 20:1043–1048

    Article  CAS  PubMed  Google Scholar 

  23. Hampel H, Frankel WL, Martin E et al (2005) Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 352:1851–1860

    Article  CAS  PubMed  Google Scholar 

  24. Pawlik TM, Raut CP, Rodriguez-Bigas MA (2004) Colorectal carcinogenesis: MSI-H versus MSI-L. Dis Markers 20:199–206

    PubMed  Google Scholar 

  25. Cruz-Correa M, Giardiello FM (2002) Diagnosis and management of hereditary colon cancer. Gastroenterol Clin North Am 31:537–549

    Article  PubMed  Google Scholar 

  26. Bleiker EM, Menko FH, Taal BG et al (2005) Screening behavior of individuals at high risk for colorectal cancer. Gastroenterology 128:280–287

    Article  PubMed  Google Scholar 

  27. Guillem JG, Wood WC, Moley JF et al (2006) ASCO/SSO review of current role of risk-reducing surgery in common hereditary cancer syndromes. J Clin Oncol 24:4642–4660

    Article  PubMed  Google Scholar 

  28. Balmana J, Balaguer F, Castellvi-Bell S et al (2008) Comparison of predictive models, clinical criteria and molecular tumour screening for the identification of patients with Lynch syndrome in a population-based cohort of colorectal cancer patients. J Med Genet 45:557–563

    Article  CAS  PubMed  Google Scholar 

  29. Sidelnikov E, Bostick RM, Flanders WD et al (2009) MutL-Homolog 1 expression and risk of incident, sporadic colorectal adenoma: search for prospective biomarkers of risk for colorectal cancer. Cancer Epidemiol Biomarkers Prev 18:1599–1609

    Article  CAS  PubMed  Google Scholar 

  30. De Jesus-Monge WE, Gonzalez-Keelan C, Cruz-Correa M (2009) Serrated adenomas. Current Gastroenterol Rep 11:420–427

    Article  Google Scholar 

  31. Vasen HF, Moslein G, Alonso A et al. (2009) Recommendations to improve identification of hereditary and familial colorectal cancer in Europe. Fam Cancer. Available via INTERNET. http://www.springerlink.com/content/u165m5k773817528/. Cited 28 Oct 2009

  32. Ponz de Leon M, Bertario L, Genuardi M et al (2007) Identification and classification of hereditary nonpolyposis colorectal cancer (Lynch syndrome): adapting old concepts to recent advancements. Report from the Italian Association for the Study of Hereditary Colorectal Tumors Consensus Group. Dis Colon Rectum 50:2126–2134

    Article  PubMed  Google Scholar 

  33. Lynch HT, Fusaro RM, Lynch PM (2006) Sebaceous skin lesions as clues to hereditary non-polyposis colorectal cancer. J Invest Dermatol 126:2158–2159

    Article  CAS  PubMed  Google Scholar 

  34. 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

    Article  PubMed  Google Scholar 

  35. de La Chapelle A (2002) Microsatellite instability phenotype of tumors: genotyping or immunohistochemistry? The jury is still out. J Clin Oncol 20:897–899

    PubMed  Google Scholar 

  36. Morales-Burgos A, Sanchez JL, Figueroa LD et al (2008) MSH-2 and MLH-1 protein expression in Muir Torre syndrome-related and sporadic sebaceous neoplasms. P R Health Sci J 27:322–327

    PubMed  Google Scholar 

  37. Molaei M, Mansoori BK, Ghiasi S et al. (2009) Colorectal cancer in Iran: immunohistochemical profiles of four mismatch repair proteins. Int J Colorectal Dis. Available via INTERNET. http://www.springerlink.com/content/932045231028jj4k/. Cited 28 Oct 2009

  38. Evans DG, Walsh S, Hill J et al (2007) Strategies for identifying hereditary nonpolyposis colon cancer. Semin Oncol 34:411–417

    Article  CAS  PubMed  Google Scholar 

  39. Hampel H, Frankel WL, Martin E et al (2008) Feasibility of screening for Lynch syndrome among patients with colorectal cancer. J Clin Oncol 26:5783–5788

    Article  PubMed  Google Scholar 

  40. Overbeek LI, Ligtenberg MJ, Willems RW et al (2008) Interpretation of immunohistochemistry for mismatch repair proteins is only reliable in a specialized setting. Am J Surg Pathol 32:1246–1251

    Article  PubMed  Google Scholar 

  41. Recommendations from the Interagency Committee for the Review of the Racial and Ethnic Standards to the Office of Management and Budget concerning changes to the standards for the classification of federal data on race and ethnicity (1997) US Office of Management and Budget. Available via INTERNET. http://www.census.gov/population/www/socdemo/race/Directive_15.html. Cited 17 Oct 2009

  42. International Data Base (2009) US Census Bureau, Population Division, Washington. http://www.census.gov/ipc/www/idb/region.php. Cited 18 Oct 2009

  43. US American Community Survey demographic and housing estimates: 2008 (2008) US Census Bureau, American Community Survey, Washington. http://factfinder.census.gov/servlet/ADPTable?_bm=y&-geo_id=01000US&-qr_name=ACS_2008_1YR_G00_DP5&-ds_name=ACS_2008_1YR_G00_&-_lang=en&-_caller=geoselect&-state=adp&-format=. Cited 16 Oct 2009

  44. Puerto Rico American Community Survey demographic and housing estimates: 2008 (2008) US Census Bureau, American Community Survey, Washington. http://factfinder.census.gov/servlet/ADPTable?_bm=y&-state=adp&-context=adp&-qr_name=ACS_2008_1YR_G00_DP5&-ds_name=ACS_2008_1YR_G00_&-tree_id=308&-_caller=geoselect&-geo_id=04000US72&-format=&-_lang=en. Cited 17 Oct 2009

  45. Curado MP, Edwards B, Shin HR et al. (2007) Cancer incidence in five continents. International Agency for Research on Cancer, Lyon. http://www-dep.iarc.fr/. Cited 20 Oct 2009

  46. Figueroa-Valles NR (2008) Boletin del Registro de Cancer. Puerto Rico Cancer Central Registry. Available via INTERNET. http://www.salud.gov.pr/RCancer/Documents/Vol%201%20No.%202.pdf. Cited 17 Oct 2009

  47. Brim H, Mokarram P, Naghibalhossaini F et al (2008) Impact of BRAF, MLH1 on the incidence of microsatellite instability high colorectal cancer in populations based study. Mol Cancer 7:68

    Article  PubMed  Google Scholar 

  48. Ashktorab H, Smoot DT, Farzanmehr H et al (2005) Clinicopathological features and microsatellite instability (MSI) in colorectal cancers from African Americans. Int J Cancer 116:914–919

    Article  CAS  PubMed  Google Scholar 

  49. Pandey V, Prabhu JS, Payal K et al (2007) Assessment of microsatellite instability in colorectal carcinoma at an Indian center. Int J Colorectal Dis 22:777–782

    Article  PubMed  Google Scholar 

  50. Ashktorab H, Brim H, Al-Riyami M et al (2008) Sporadic colon cancer: mismatch repair immunohistochemistry and microsatellite instability in Omani subjects. Dig Dis Sci 53:2723–2731

    Article  CAS  PubMed  Google Scholar 

  51. Erdamar S, Ucaryilmaz E, Demir G et al (2007) Importance of MutL homologue MLH1 and MutS homologue MSH2 expression in Turkish patients with sporadic colorectal cancer. World J Gastroenterol 13:4437–4444

    CAS  PubMed  Google Scholar 

  52. Jin HY, Liu X, Lin VK et al (2008) Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer. BMC Cancer 8:44

    Article  PubMed  CAS  Google Scholar 

  53. Jensen LH, Lindebjerg J, Byriel L et al (2008) Strategy in clinical practice for classification of unselected colorectal tumours based on mismatch repair deficiency. Colorectal Dis 10:490–497

    Article  CAS  PubMed  Google Scholar 

  54. Boardman LA, Lanier AP, French AJ et al (2007) Frequency of defective DNA mismatch repair in colorectal cancer among the Alaska Native people. Cancer Epidemiol Biomarkers Prev 16:2344–2350

    Article  CAS  PubMed  Google Scholar 

  55. Wright CL, Stewart ID (2003) Histopathology and mismatch repair status of 458 consecutive colorectal carcinomas. Am J Surg Pathol 27:1393–1406

    Article  PubMed  Google Scholar 

  56. Coggins RP, Cawkwell L, Bell SM et al (2005) Association between family history and mismatch repair in colorectal cancer. Gut 54:636–642

    Article  CAS  PubMed  Google Scholar 

  57. 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 99:244–252

    Article  CAS  PubMed  Google Scholar 

  58. Piñol V, Castells A, Andreu M et al (2005) Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA 293:1986–1994

    Article  PubMed  Google Scholar 

  59. Terdiman JP, Gum JR Jr, Conrad PG et al (2001) Efficient detection of hereditary nonpolyposis colorectal cancer gene carriers by screening for tumor microsatellite instability before germline genetic testing. Gastroenterology 120:21–30

    Article  CAS  PubMed  Google Scholar 

  60. Christensen M, Katballe N, Wikman F et al (2002) Antibody-based screening for hereditary nonpolyposis colorectal carcinoma compared with microsatellite analysis and sequencing. Cancer 95:2422–2430

    Article  CAS  PubMed  Google Scholar 

  61. Wahlberg SS, Schmeits J, Thomas G et al (2002) Evaluation of microsatellite instability and immunohistochemistry for the prediction of germ-line MSH2 and MLH1 mutations in hereditary nonpolyposis colon cancer families. Cancer Res 62:3485–3492

    CAS  PubMed  Google Scholar 

  62. Park JG, Vasen HF, Park YJ et al (2002) Suspected HNPCC and Amsterdam criteria II: evaluation of mutation detection rate, an international collaborative study. Int J Colorectal Dis 17:109–114

    Article  PubMed  Google Scholar 

  63. Hitchins M, Williams R, Cheong K et al (2005) MLH1 germline epimutations as a factor in hereditary nonpolyposis colorectal cancer. Gastroenterology 129:1392–1399

    Article  CAS  PubMed  Google Scholar 

  64. Bermejo JL, Eng C, Hemminki K (2005) Cancer characteristics in Swedish families fulfilling criteria for hereditary nonpolyposis colorectal cancer. Gastroenterology 129:1889–1899

    Article  PubMed  Google Scholar 

  65. Woerner SM, Kloor M, Mueller A et al (2005) Microsatellite instability of selective target genes in HNPCC-associated colon adenomas. Oncogene 24:2525–2535

    Article  CAS  PubMed  Google Scholar 

  66. Plaschke J, Engel C, Kruger S et al (2004) Lower incidence of colorectal cancer and later age of disease onset in 27 families with pathogenic MSH6 germline mutations compared with families with MLH1 or MSH2 mutations: the German Hereditary Nonpolyposis Colorectal Cancer Consortium. J Clin Oncol 22:4486–4494

    Article  CAS  PubMed  Google Scholar 

  67. Lim SB, Jeong SY, Lee MR et al (2004) Prognostic significance of microsatellite instability in sporadic colorectal cancer. Int J Colorectal Dis 19:533–537

    Article  PubMed  Google Scholar 

  68. Cruz-Correa M, Giardiello FM (2003) Familial adenomatous polyposis. Gastrointest Endosc 58:885–894

    Article  PubMed  Google Scholar 

  69. Half ED, Bercovich D, Rozen P (2009) Familial adenomatous polyposis. Orphanet J Rare Dis 4:22

    Article  PubMed  Google Scholar 

  70. Rozen P, Macrae F (2006) Familial adenomatous polyposis: the practical applications of clinical and molecular screening. Fam Cancer 5:227–235

    Article  CAS  PubMed  Google Scholar 

  71. Puerto Rico general demographic characteristics: 2005 (2005) US Census Bureau, American Community Survey, Washington. http://factfinder.census.gov/servlet/ADPTable?_bm=y&-state=adp&-context=adp&-qr_name=ACS_2005_EST_G00_DP1&-ds_name=ACS_2005_EST_G00_&-tree_id=305&-redoLog=true&-all_geo_types=N&-_caller=geoselect&-geo_id=04000US72&-format=&-_lang=en. Cited 16 Oct 2009

  72. 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 96:261–268

    Article  CAS  PubMed  Google Scholar 

  73. Fleming ID, Cooper JS, Henson DE et al (eds) (1997) AJCC cancer staging manual, 5th edn. Lippincott-Raven, Philadelphia

    Google Scholar 

  74. Soto-Salgado M, Suarez E, Calo W et al (2009) Incidence and mortality rates for colorectal cancer in Puerto Rico and among hispanics, non-hispanic whites, and non-hispanic blacks in the United States, 1998–2002. Cancer 115:3016–3023

    Article  PubMed  Google Scholar 

  75. Jover R, Zapater P, Castells A et al (2009) The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status. Eur J Cancer 45:365–373

    Article  CAS  PubMed  Google Scholar 

  76. Carethers JM, Smith EJ, Behling CA et al (2004) Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer. Gastroenterology 126:394–401

    Article  CAS  PubMed  Google Scholar 

  77. 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 349:247–257

    Article  CAS  PubMed  Google Scholar 

  78. Bertagnolli MM, Niedzwiecki D, Compton CC et al (2009) Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, fluorouracil, and leucovorin in stage III colon cancer: cancer and leukemia group B protocol 89803. J Clin Oncol 27:1814–1821

    Article  CAS  PubMed  Google Scholar 

  79. Grover S, Syngal S (2009) Genetic testing in gastroenterology: Lynch syndrome. Best Pract Res Clin Gastroenterol 23:185–196

    Article  CAS  PubMed  Google Scholar 

  80. Beiner ME, Rosen B, Fyles A et al (2006) Endometrial cancer risk is associated with variants of the mismatch repair genes MLH1 and MSH2. Cancer Epidemiol Biomarkers Prev 15:1636–1640

    Article  CAS  PubMed  Google Scholar 

  81. Yoon SN, Ku JL, Shin YK et al (2008) Hereditary nonpolyposis colorectal cancer in endometrial cancer patients. Int J Cancer 122:1077–1081

    Article  CAS  PubMed  Google Scholar 

  82. Park JG, Kim DW, Hong CW et al (2006) Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study. Clin Cancer Res 12:3389–3393

    Article  CAS  PubMed  Google Scholar 

  83. Scaife CL, Rodriguez-Bigas MA (2003) Lynch syndrome: implications for the surgeon. Clin Colorectal Cancer 3:92–98

    Article  PubMed  Google Scholar 

  84. Watson P, Riley B (2005) The tumor spectrum in the Lynch syndrome. Fam Cancer 4:245–248

    Article  PubMed  Google Scholar 

  85. Watson P, Lynch HT (2001) Cancer risk in mismatch repair gene mutation carriers. Fam Cancer 1:57–60

    Article  CAS  PubMed  Google Scholar 

  86. Manchanda R, Menon U, Michaelson-Cohen R et al (2009) Hereditary non-polyposis colorectal cancer or Lynch syndrome: the gynaecological perspective. Curr Opin Obstet Gynecol 21:31–38

    Article  PubMed  Google Scholar 

  87. Brown GJ, St John DJ, Macrae FA et al (2001) Cancer risk in young women at risk of hereditary nonpolyposis colorectal cancer: implications for gynecologic surveillance. Gynecol Oncol 80:346–349

    Article  CAS  PubMed  Google Scholar 

  88. Schmeler KM, Lu KH (2008) Gynecologic cancers associated with Lynch syndrome/HNPCC. Clin Transl Oncol 10:313–317

    Article  CAS  PubMed  Google Scholar 

  89. Dionigi G, Bianchi V, Villa F et al (2007) Differences between familial and sporadic forms of colorectal cancer with DNA microsatellite instability. Surg Oncol 16:S37–S42

    Article  PubMed  Google Scholar 

  90. Aaltonen LA, Peltomaki P, Mecklin JP et al (1994) Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients. Cancer Res 54:1645–1648

    CAS  PubMed  Google Scholar 

  91. Herman JG, Umar A, Polyak K et al (1998) Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci U S A 95:6870–6875

    Article  CAS  PubMed  Google Scholar 

  92. Kuismanen SA, Holmberg MT, Salovaara R et al (2000) Genetic and epigenetic modification of MLH1 accounts for a major share of microsatellite-unstable colorectal cancers. Am J Pathol 156:1773–1779

    CAS  PubMed  Google Scholar 

  93. Gryfe R, Gallinger S (2001) Microsatellite instability, mismatch repair deficiency, and colorectal cancer. Surgery 130:17–20

    Article  CAS  PubMed  Google Scholar 

  94. Lothe RA, Peltomaki P, Meling GI et al (1993) Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. Cancer Res 53:5849–5852

    CAS  PubMed  Google Scholar 

  95. O’Brien MJ (2007) Hyperplastic and serrated polyps of the colorectum. Gastroenterol Clin North Am 36:947–968 viii

    Article  PubMed  Google Scholar 

  96. Esteller M, Fraga MF, Guo M et al (2001) DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis. Hum Mol Genet 10:3001–3007

    Article  CAS  PubMed  Google Scholar 

  97. Chirieac LR, Chen L, Catalano PJ et al (2005) Phenotype of microsatellite-stable colorectal carcinomas with CpG island methylation. Am J Surg Pathol 29:429–436

    Article  PubMed  Google Scholar 

  98. van Rijnsoever M, Grieu F, Elsaleh H et al (2002) Characterisation of colorectal cancers showing hypermethylation at multiple CpG islands. Gut 51:797–802

    Article  PubMed  Google Scholar 

  99. Kambara T, Simms LA, Whitehall VL et al (2004) BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut 53:1137–1144

    Article  CAS  PubMed  Google Scholar 

  100. Al-Kuraya KS, Bavi PP, Ezzat AA et al (2006) Colorectal carcinoma from Saudi Arabia. Analysis of MLH-1, MSH-2 and p53 genes by immunohistochemistry and tissue microarray analysis. Saudi Med J 27:323–328

    PubMed  Google Scholar 

  101. Samowitz WS, Curtin K, Ma KN et al (2001) Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level. Cancer Epidemiol Biomarkers Prev 10:917–923

    CAS  PubMed  Google Scholar 

  102. Chen JR, Chiang JM, Changchien CR et al (2008) Mismatch repair protein expression in Amsterdam II criteria-positive patients in Taiwan. Br J Surg 95:102–110

    Article  CAS  PubMed  Google Scholar 

  103. Gryfe R, Kim H, Hsieh ET et al (2000) Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 342:69–77

    Article  CAS  PubMed  Google Scholar 

  104. Mecklin JP, Jarvinen HJ (1986) Clinical features of colorectal carcinoma in cancer family syndrome. Dis Colon Rectum 29:160–164

    Article  CAS  PubMed  Google Scholar 

  105. Watson N, Grieu F, Morris M et al (2007) Heterogeneous staining for mismatch repair proteins during population-based prescreening for hereditary nonpolyposis colorectal cancer. J Mol Diagn 9:472–478

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the National Institutes of Health (NIH) National Center for Research Resources, grants R25 RR 017589, P20 RR 011126-13, and G12 RR 003051-22; and NIH National Cancer Institute, grants K07 CA 092445, K22 CA 115913-02, and U54 CA 096297. S.R.H. is the Frederick F. Becker Distinguished University Chair in Cancer Research from The University of Texas. We thank the Department of Pathology of the PRMC and the HOIGM for tissue access; the Department of Medical Records of the PRMC and the HOIGM and the HOIGM cancer registry for data access; Mr. Nelson Santiago and Mrs. Janet E. Quiñones for laboratory technical support; Mr. Alexis A. Florian-Ayala and Mr. Alejandro Lopez-Araujo for data collection and laboratory technical support; Kerry Sieger for MSI evaluation and BRAF gene sequencing; and Dr. Sara S. Strom, Dr. Francis M. Giardiello, Dr. Elena Martinez-Stoffel, Prof. Vivianna M. De Jesus-Monge, and the faculty and scholars of the University of Puerto Rico Master of Science in Clinical Research Program for critical feedback. This work was done as fulfillment for the studies for a graduate degree from the University of Puerto Rico Medical Sciences Campus by Wilfredo E. De Jesus-Monge.

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Authors and Affiliations

  1. Master of Science in Clinical Research Program, University of Puerto Rico, San Juan, PR, USA

    Wilfredo E. De Jesus-Monge

  2. University of Massachusetts Medical School, Worcester, MA, USA

    Wilfredo E. De Jesus-Monge

  3. Department of Medicine, University of Puerto Rico, San Juan, PR, USA

    Wilfredo E. De Jesus-Monge & Marcia Cruz-Correa

  4. Clinical Research Center, Medical Sciences Campus, P.O. Box 365067, San Juan, PR, 00936-5067, USA

    Marcia Cruz-Correa

  5. Department of Pathology and Laboratory Medicine, University of Puerto Rico, San Juan, PR, USA

    Carmen Gonzalez-Keelan

  6. Comprehensive Cancer Center, University of Puerto Rico, San Juan, PR, USA

    Ronghua Zhao & Marcia Cruz-Correa

  7. Department of Surgery, University of Saskatchewan College of Medicine, Saskatoon, SK, Canada

    Ronghua Zhao

  8. Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Stanley R. Hamilton

  9. Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Miguel Rodriguez-Bigas & Marcia Cruz-Correa

  10. Department of Biochemistry, University of Puerto Rico, San Juan, PR, USA

    Marcia Cruz-Correa

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  1. Wilfredo E. De Jesus-Monge
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Correspondence to Marcia Cruz-Correa.

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De Jesus-Monge, W.E., Gonzalez-Keelan, C., Zhao, R. et al. Mismatch repair protein expression and colorectal cancer in Hispanics from Puerto Rico. Familial Cancer 9, 155–166 (2010). https://doi.org/10.1007/s10689-009-9310-4

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