Skip to main content

Advertisement

SpringerLink
Log in

Predictive and Prognostic Markers in Colorectal Cancer

  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Colorectal cancer (CRC) has a complex pathogenesis involving multiple sequential steps with accumulation of genetic alterations including mutations, gene amplification, and epigenetic changes. Treatment of CRC has undergone a paradigm shift over the past decade due in part to a better understanding of the biology of the disease and development of newer drugs including biologic agents. In the era of personalized medicine, it is attractive to investigate the molecular pathways leading to colorectal cancer tumorigenesis, thus raising the possibility of identifying novel therapeutic targets. It has intuitive appeal to hypothesize that biomarkers that have prognostic and/or predictive value are those that are intimately connected to the pathogenesis of CRC. In this article, we focus on prognostic and predictive markers in CRC that have a substantial body of data in support of their potential role in routine clinical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.

    Article  PubMed  Google Scholar 

  2. Worthley DL, Whitehall VL, Spring KJ, Leggett BA. Colorectal carcinogenesis: road maps to cancer. World J Gastroenterol. 2007;13:3784–91.

    PubMed  CAS  Google Scholar 

  3. Spirio L, Otterud B, Stauffer D, et al. Linkage of a variant or attenuated form of adenomatous polyposis coli to the adenomatous polyposis coli (APC) locus. Am J Hum Genet. 1992;51:92–100.

    PubMed  CAS  Google Scholar 

  4. Bronner CE, Baker SM, Morrison PT, et al. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature. 1994;368:258–61.

    Article  PubMed  CAS  Google Scholar 

  5. Fishel R, Lescoe MK, Rao MR, et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993;75:1027–38.

    Article  PubMed  CAS  Google Scholar 

  6. Leach FS, Nicolaides NC, Papadopoulos N, et al. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993;75:1215–25.

    Article  PubMed  CAS  Google Scholar 

  7. Miyaki M, Konishi M, Tanaka K, et al. Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. Nat Genet. 1997;17(3):271–2.

    Article  PubMed  CAS  Google Scholar 

  8. Papadopoulos N, Nicolaides NC, Wei YF, et al. Mutation of a mutL homolog in hereditary colon cancer. Science. 1994;263:1625–9.

    Article  PubMed  CAS  Google Scholar 

  9. Boland CR, Koi M, Chang DK, Carethers JM. The biochemical basis of microsatellite instability and abnormal immunohistochemistry and clinical behavior in Lynch syndrome: from bench to bedside. Fam Cancer. 2008;7:41–52.

    Article  PubMed  CAS  Google Scholar 

  10. Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96(4):261–8.

    Article  PubMed  CAS  Google Scholar 

  11. Lynch HT, Lynch JF, Lynch PM, Attard T. Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management. Fam Cancer. 2008;7:27–39.

    Article  PubMed  CAS  Google Scholar 

  12. Boland CR, Thibodeau SN, Hamilton SR, et al. 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. 1998;58:5248–57.

    PubMed  CAS  Google Scholar 

  13. Veigl ML, Kasturi L, Olechnowicz J, et al. Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers. Proc Natl Acad Sci USA. 1998;95:8698–702.

    Article  PubMed  CAS  Google Scholar 

  14. Lindor NM, Burgart LJ, Leontovich O, et al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol. 2002;20:1043–8.

    Article  PubMed  CAS  Google Scholar 

  15. Kim H, Jen J, Vogelstein B, Hamilton SR. Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol. 1994;145:148–56.

    PubMed  CAS  Google Scholar 

  16. Lothe RA, Peltomaki P, Meling GI, et al. Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. Cancer Res. 1993;53:5849–52.

    PubMed  CAS  Google Scholar 

  17. Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993;260:816–9.

    Article  PubMed  CAS  Google Scholar 

  18. Ribic CM, Sargent DJ, Moore MJ, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003;349:247–57.

    Article  PubMed  CAS  Google Scholar 

  19. •• Sargent DJ, Marsoni S, Monges G, et al.: Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 2010, 28: 3219–26. This paper provides a strong rationale for stratifying high-risk stage II patients based on MSI status before administering adjuvant chemotherapy.

    Article  PubMed  CAS  Google Scholar 

  20. Morris M, Platell C, Iacopetta B. Tumor-infiltrating lymphocytes and perforation in colon cancer predict positive response to 5-fluorouracil chemotherapy. Clin Cancer Res. 2008;14:1413–7.

    Article  PubMed  CAS  Google Scholar 

  21. Arnold CN, Goel A, Boland CR. Role of hMLH1 promoter hypermethylation in drug resistance to 5-fluorouracil in colorectal cancer cell lines. Int J Cancer. 2003;106:66–73.

    Article  PubMed  CAS  Google Scholar 

  22. Fischer F, Baerenfaller K, Jiricny J. 5-Fluorouracil is efficiently removed from DNA by the base excision and mismatch repair systems. Gastroenterology. 2007;133:1858–68.

    Article  PubMed  CAS  Google Scholar 

  23. Andre T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350:2343–51.

    Article  PubMed  CAS  Google Scholar 

  24. •• Roth AD, Tejpar S, Delorenzi M, et al.: Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60–00 trial. J Clin Oncol 2009, 28: 466–74. This large study demonstrates 1) a lack of prognostic utility for KRAS in stage II/III colon cancer patients; and 2) the prognostic value of BRAF in MSI-L/stable patients in terms of overall survival.

    Article  PubMed  Google Scholar 

  25. Fearon ER, Cho KR, Nigro JM, et al. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science. 1990;247:49–56.

    Article  PubMed  CAS  Google Scholar 

  26. Thiagalingam S, Lengauer C, Leach FS, et al. Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers. Nat Genet. 1996;13:343–6.

    Article  PubMed  CAS  Google Scholar 

  27. Vogelstein B, Fearon ER, Hamilton SR, et al. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988;319:525–32.

    Article  PubMed  CAS  Google Scholar 

  28. Watanabe T, Wu TT, Catalano PJ, et al. Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med. 2001;344:1196–206.

    Article  PubMed  CAS  Google Scholar 

  29. Jen J, Kim H, Piantadosi S, et al. Allelic loss of chromosome 18q and prognosis in colorectal cancer. N Engl J Med. 1994;331:213–21.

    Article  PubMed  CAS  Google Scholar 

  30. Carethers JM, Hawn MT, Greenson JK, et al. Prognostic significance of allelic lost at chromosome 18q21 for stage II colorectal cancer. Gastroenterology. 1998;114:1188–95.

    Article  PubMed  CAS  Google Scholar 

  31. Barratt PL, Seymour MT, Stenning SP, et al. DNA markers predicting benefit from adjuvant fluorouracil in patients with colon cancer: a molecular study. Lancet. 2002;360:1381–91.

    Article  PubMed  CAS  Google Scholar 

  32. Shibata D, Reale MA, Lavin P, et al. The DCC protein and prognosis in colorectal cancer. N Engl J Med. 1996;335:1727–32.

    Article  PubMed  CAS  Google Scholar 

  33. Roth AD, Tejpar S, Yan P, et al. Stage-specific prognostic value of molecular markers in colon cancer: results of the translational study on the PETACC 3-EORTC 40993-SAKK 60–00 trial. J Clin Oncol. 2009;27:4002.

    Article  Google Scholar 

  34. Ogino S, Nosho K, Irahara N, et al. Prognostic significance and molecular associations of 18q loss of heterozygosity: a cohort study of microsatellite stable colorectal cancers. J Clin Oncol. 2009;27:4591–8.

    Article  PubMed  Google Scholar 

  35. Bos JL, Fearon ER, Hamilton SR, et al. Prevalence of ras gene mutations in human colorectal cancers. Nature. 1987;327:293–7.

    Article  PubMed  CAS  Google Scholar 

  36. Bourne HR, Sanders DA, McCormick F. The GTPase superfamily: conserved structure and molecular mechanism. Nature. 1991;349:117–27.

    Article  PubMed  CAS  Google Scholar 

  37. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2:127–37.

    Article  PubMed  CAS  Google Scholar 

  38. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61:759–67.

    Article  PubMed  CAS  Google Scholar 

  39. Artale S, Sartore-Bianchi A, Veronese SM, et al. Mutations of KRAS and BRAF in primary and matched metastatic sites of colorectal cancer. J Clin Oncol. 2008;26(25):4217–9.

    Article  PubMed  Google Scholar 

  40. Zauber P, Sabbath-Solitare M, Marotta SP, Bishop DT. Molecular changes in the Ki-ras and APC genes in primary colorectal carcinoma and synchronous metastases compared with the findings in accompanying adenomas. Mol Pathol. 2003;56:137–40.

    Article  PubMed  CAS  Google Scholar 

  41. Bos JL. Ras oncogenes in human cancer: a review. Cancer Res. 1989;49:4682–9.

    PubMed  CAS  Google Scholar 

  42. Edkins S, O'Meara S, Parker A, et al. Recurrent KRAS codon 146 mutations in human colorectal cancer. Cancer Biol Ther. 2006;5:928–32.

    Article  PubMed  CAS  Google Scholar 

  43. Andreyev HJ, Norman AR, Cunningham D, et al. Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study. Br J Cancer. 2001;85:692–6.

    Article  PubMed  CAS  Google Scholar 

  44. Barault L, Veyrie N, Jooste V, et al. Mutations in the RAS-MAPK, PI(3)K (phosphatidylinositol-3-OH kinase) signaling network correlate with poor survival in a population-based series of colon cancers. Int J Cancer. 2008;122:2255–9.

    Article  PubMed  CAS  Google Scholar 

  45. Dix BR, Robbins P, Soong R, et al. The common molecular genetic alterations in Dukes' B and C colorectal carcinomas are not short-term prognostic indicators of survival. Int J Cancer. 1994;59:747–51.

    Article  PubMed  CAS  Google Scholar 

  46. Esteller M, Gonzalez S, Risques RA, et al. K-ras and p16 aberrations confer poor prognosis in human colorectal cancer. J Clin Oncol. 2001;19:299–304.

    PubMed  CAS  Google Scholar 

  47. •• Karapetis CS, Khambata-Ford S, Jonker DJ, et al.: K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008, 359: 1757–65. This study demonstrates the predictive value of KRAS mutations in determining response to anti-EGFR–targeted therapy.

    Article  PubMed  CAS  Google Scholar 

  48. Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:1626–34.

    Article  PubMed  CAS  Google Scholar 

  49. Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007;25:1658–64.

    Article  PubMed  Google Scholar 

  50. Scaltriti M, Baselga J. The epidermal growth factor receptor pathway: a model for targeted therapy. Clin Cancer Res. 2006;12:5268–72.

    Article  PubMed  CAS  Google Scholar 

  51. Chung KY, Shia J, Kemeny NE, et al. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol. 2005;23:1803–10.

    Article  PubMed  CAS  Google Scholar 

  52. Saltz LB, Meropol NJ, Loehrer Sr PJ, et al. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol. 2004;22:1201–8.

    Article  PubMed  CAS  Google Scholar 

  53. Barber TD, Vogelstein B, Kinzler KW, Velculescu VE. Somatic mutations of EGFR in colorectal cancers and glioblastomas. N Engl J Med. 2004;351(27):2883.

    Article  PubMed  CAS  Google Scholar 

  54. Moroni M, Veronese S, Benvenuti S, et al. Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol. 2005;6:279–86.

    Article  PubMed  CAS  Google Scholar 

  55. Cappuzzo F, Finocchiaro G, Rossi E, et al. EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients. Ann Oncol. 2008;19:717–23.

    Article  PubMed  CAS  Google Scholar 

  56. Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, et al. Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res. 2007;67:2643–8.

    Article  PubMed  CAS  Google Scholar 

  57. Lievre A, Bachet JB, Le Corre D, et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006;66:3992–5.

    Article  PubMed  CAS  Google Scholar 

  58. Albitar M, Yeh C, Ma W. K-ras mutations and cetuximab in colorectal cancer. N Engl J Med. 2009;360(8):834. author reply 835–6.

    PubMed  CAS  Google Scholar 

  59. De Roock W, Lambrechts D, Tejpar S. K-ras mutations and cetuximab in colorectal cancer. N Engl J Med. 2009;360(8):834. author reply 835–6.

    PubMed  Google Scholar 

  60. Bokemeyer C, Bondarenko I, Makhson A, et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2009;27:663–71.

    Article  PubMed  CAS  Google Scholar 

  61. Van Cutsem E, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408–17.

    Article  PubMed  Google Scholar 

  62. Loupakis F, Ruzzo A, Cremolini C, et al. KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br J Cancer. 2009;101:715–21.

    Article  PubMed  CAS  Google Scholar 

  63. De Roock W, Claes B, Bernasconi D, et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010;11:753–62.

    Article  PubMed  Google Scholar 

  64. Irahara N, Baba Y, Nosho K, et al.: NRAS mutations are rare in colorectal cancer. Diagn Mol Pathol. 19:157–63.

  65. Loupakis F, Pollina L, Stasi I, et al. PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer. J Clin Oncol. 2009;27:2622–9.

    Article  PubMed  CAS  Google Scholar 

  66. De Roock W, Jonker DJ, Di Nicolantonio F, et al. Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. Jama. 1812;304:1812–20.

    Article  Google Scholar 

  67. Janakiraman M, Vakiani E, Zeng Z, et al.: Genomic and biological characterization of exon 4 KRAS mutations in human cancer. Cancer Res. 70:5901–11.

  68. Peyssonnaux C, Eychene A. The Raf/MEK/ERK pathway: new concepts of activation. Biol Cell. 2001;93:53–62.

    Article  PubMed  CAS  Google Scholar 

  69. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–54.

    Article  PubMed  CAS  Google Scholar 

  70. Kim IJ, Kang HC, Jang SG, et al. Oligonucleotide microarray analysis of distinct gene expression patterns in colorectal cancer tissues harboring BRAF and K-ras mutations. Carcinogenesis. 2006;27:392–404.

    Article  PubMed  CAS  Google Scholar 

  71. Weisenberger DJ, Siegmund KD, Campan M, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006;38:787–93.

    Article  PubMed  CAS  Google Scholar 

  72. Rajagopalan H, Bardelli A, Lengauer C, et al. Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature. 2002;418:934.

    Article  PubMed  CAS  Google Scholar 

  73. Wang L, Cunningham JM, Winters JL, et al. BRAF mutations in colon cancer are not likely attributable to defective DNA mismatch repair. Cancer Res. 2003;63:5209–12.

    PubMed  CAS  Google Scholar 

  74. Samowitz WS, Sweeney C, Herrick J, et al. Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res. 2005;65:6063–9.

    Article  PubMed  CAS  Google Scholar 

  75. Ogino S, Nosho K, Kirkner GJ, et al. CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. Gut. 2009;58:90–6.

    Article  PubMed  Google Scholar 

  76. Farina-Sarasqueta A, van Lijnschoten G, Moerland E, et al.: The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients. Ann Oncol. 2010: 25.

  77. Di Nicolantonio F, Martini M, Molinari F, et al. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008;26:5705–12.

    Article  PubMed  Google Scholar 

  78. Tol J, Nagtegaal ID, Punt CJ. BRAF mutation in metastatic colorectal cancer. N Engl J Med. 2009;361(1):98–9.

    Article  PubMed  CAS  Google Scholar 

  79. Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007;129:1261–74.

    Article  PubMed  CAS  Google Scholar 

  80. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006;7:606–19.

    Article  PubMed  CAS  Google Scholar 

  81. Samuels Y, Wang Z, Bardelli A, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004;304:11.

    Article  Google Scholar 

  82. Samuels Y, Velculescu VE. Oncogenic mutations of PIK3CA in human cancers. Cell Cycle. 2004;3:1221–4.

    Article  PubMed  CAS  Google Scholar 

  83. Kato S, Iida S, Higuchi T, et al. PIK3CA mutation is predictive of poor survival in patients with colorectal cancer. Int J Cancer. 2007;121:1771–8.

    Article  PubMed  CAS  Google Scholar 

  84. Nosho K, Kawasaki T, Ohnishi M, et al. PIK3CA mutation in colorectal cancer: relationship with genetic and epigenetic alterations. Neoplasia. 2008;10:534–41.

    PubMed  CAS  Google Scholar 

  85. Ogino S, Nosho K, Kirkner GJ, et al. PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer. J Clin Oncol. 2009;27:1477–84.

    Article  PubMed  CAS  Google Scholar 

  86. Velho S, Oliveira C, Ferreira A, et al. The prevalence of PIK3CA mutations in gastric and colon cancer. Eur J Cancer. 2005;41:1649–54.

    Article  PubMed  CAS  Google Scholar 

  87. He Y, Van't Veer LJ, Mikolajewska-Hanclich I, et al. PIK3CA mutations predict local recurrences in rectal cancer patients. Clin Cancer Res. 2009;15:6956–62.

    Article  PubMed  CAS  Google Scholar 

  88. Stokoe D: Pten. Curr Biol 2001, 11.

  89. Parsons DW, Wang TL, Samuels Y, et al. Colorectal cancer: mutations in a signalling pathway. Nature. 2005;436:792.

    Article  PubMed  CAS  Google Scholar 

  90. Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2:489–501.

    Article  PubMed  CAS  Google Scholar 

  91. Laurent-Puig P, Cayre A, Manceau G, et al. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol. 2009;27:5924–30.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosure

B. George: none; S. Kopetz: consultant for Bristol-Myers Squibb, Roche/Genentech, Circadian, Sanofi-Aventis, and AstraZeneca.

Author information

Authors and Affiliations

  1. Division of Hematology/Medical Oncology, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Milwaukee, WI, 53226, USA

    Ben George

  2. GI Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Faculty Center (FC 10.2004), 1515 Holcombe Blvd., Unit 0426, Houston, TX, 77030, USA

    Scott Kopetz

Authors
  1. Ben George
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Scott Kopetz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Scott Kopetz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

George, B., Kopetz, S. Predictive and Prognostic Markers in Colorectal Cancer. Curr Oncol Rep 13, 206–215 (2011). https://doi.org/10.1007/s11912-011-0162-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11912-011-0162-3

Keywords

Search

Navigation