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Recent approaches to identifying biomarkers for high-risk stage II colon cancer

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Abstract

The use of adjuvant chemotherapy for stage II colon cancer remains controversial. The accurate assessment of the risk factors associated with recurrence in patients with stage II disease is the key to identifying the patients that are most likely to benefit from adjuvant chemotherapy. Recent guidelines advocate that adjuvant chemotherapy for high-risk stage II colon cancer should take into account factors such as the T stage, number of lymph nodes examined, tumor differentiation, and tumor perforation. In addition to these clinicopathological factors, there has also been intense interest in the identification of new prognostic or predictive biomarkers that can improve outcomes through better patient classification and selection for adjuvant chemotherapy. Recent advances in the field of molecular genetics have led to the identification of specific biomarkers involved in colorectal cancer progression, whereas gene expression microarray technology has led to the identification of molecular profiles able to predict recurrence or benefit from adjuvant chemotherapy. However, none of these has yet been validated in large prospective clinical trials. In this article, we review the current status of prognostic and predictive biomarkers for stage II colon cancer and provide an update on the most recent developments.

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References

  1. Buyse M, Piedbois P. Should Dukes’ B patients receive adjuvant therapy? A statistical perspective. Semin Oncol. 2001;28:20–4.

    Article  PubMed  CAS  Google Scholar 

  2. Figueredo A, Coombes ME, Mukherjee S. Adjuvant therapy for completely resected stage II colon cancer. Cochrane Database Syst Rev 2008;16:CD005390.

    Google Scholar 

  3. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti d. AJCC cancer staging manual. 7th ed. New York: Springer; 2010.

    Google Scholar 

  4. Andre T, Sargent D, Tabernero J, O’Connell M, Buyse M, Sobrero A, et al. Current issues in adjuvant treatment of stage II colon cancer. Ann Surg Oncol. 2006;13:887–98.

    Article  PubMed  Google Scholar 

  5. Morris EJ, Maughan NJ, Forman D, Quirke P. Who to treat with adjuvant therapy in Dukes B/stage II colorectal cancer? The need for high quality pathology. Gut. 2007;56:1419–25.

    Article  PubMed  Google Scholar 

  6. Nelson H, Petrelli N, Carlin A, Couture J, Fleshman J, Guillem J, et al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst. 2001;93:583–96.

    Article  PubMed  CAS  Google Scholar 

  7. Benson AB 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22:3408–19.

    Article  PubMed  Google Scholar 

  8. Labianca R, Nordlinger B, Beretta GD, Brouquet A. ESMO Guidelines Working Group. Primary colon cancer: ESMO Clinical Practice Guidelines for diagnosis, adjuvant treatment and follow-up. Ann Oncol. 2010;21(Suppl 5):v70–7.

    Article  PubMed  Google Scholar 

  9. Engstrom PF, Arnoletti JP, Benson AB 3rd, Chen YJ, Choti MA, Cooper HS, et al. NCCN Clinical Practice Guidelines in Oncology: colon cancer. J Natl Compr Canc Netw. 2009;7:778–831.

    PubMed  Google Scholar 

  10. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, et al. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988;319:525–32.

    Article  PubMed  CAS  Google Scholar 

  11. Rajagopalan H, Nowak MA, Vogelstein B, Lengauer C. The significance of unstable chromosomes in colorectal cancer. Nat Rev Cancer. 2003;3:695–701.

    Article  PubMed  CAS  Google Scholar 

  12. Tejpar S, Bertagnolli M, Bosman F, Lenz HJ, Garraway L, Waldman F, et al. Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery. Oncologist. 2010;15:390–404.

    Article  PubMed  CAS  Google Scholar 

  13. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, 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 

  14. Gryfe R, Kim H, Hsieh ET, Aronson MD, Holowaty EJ, Bull SB, et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med. 2000;342:69–77.

    Article  PubMed  CAS  Google Scholar 

  15. Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, 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 

  16. Lanza G, Gafa R, Santini A, Maestri I, Guerzoni L, Cavazzini L. Immunohistochemical test for MLH1 and MSH2 expression predicts clinical outcome in stage II and III colorectal cancer patients. J Clin Oncol. 2006;24:2359–67.

    Article  PubMed  CAS  Google Scholar 

  17. Halling KC, French AJ, McDonnell SK, Burgart LJ, Schaid DJ, Peterson BJ, et al. Microsatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers. J Natl Cancer Inst. 1999;91:1295–303.

    Article  PubMed  CAS  Google Scholar 

  18. Roth AD, Tejpar S, Delorenzi M, Yan P, Fiocca R, Klingbiel D, 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. 2010;28:466–74.

    Article  PubMed  CAS  Google Scholar 

  19. Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 2005;23:609–18.

    Article  PubMed  CAS  Google Scholar 

  20. Sargent DJ, Marsoni S, Monges G, Thibodeau SN, Labianca R, Hamilton SR, 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.

    Article  PubMed  CAS  Google Scholar 

  21. Eastern Cooperative Oncology Group 5202 (NCT00217737). Oxaliplatin, leucovorin, and fluorouracil with or without bevacizumab in treating patients who have undergone surgery for stage II colon cancer. http://clinicaltrials.gov/ct2/show/NCT00217737?term=E5202&rank=1.

  22. Popat S, Houlston RS. A systematic review and meta-analysis of the relationship between chromosome 18q genotype, DCC status and colorectal cancer prognosis. Eur J Cancer. 2005;41:2060–70.

    Article  PubMed  CAS  Google Scholar 

  23. Sarli L, Bottarelli L, Bader G, Iusco D, Pizzi S, Costi R, et al. Association between recurrence of sporadic colorectal cancer, high level of microsatellite instability, and loss of heterozygosity at chromosome 18q. Dis Colon Rectum. 2004;47:1467–82.

    Article  PubMed  Google Scholar 

  24. Chang SC, Lin JK, Lin TC, Liang WY. Loss of heterozygosity: an independent prognostic factor of colorectal cancer. World J Gastroenterol. 2005;11:778–84.

    PubMed  CAS  Google Scholar 

  25. Watanabe T, Wu TT, Catalano PJ, Ueki T, Satriano R, Haller DG, 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 

  26. Martinez-Lopez E, Abad A, Font A, Monzo M, Ojanguren I, Pifarre A, et al. Allelic loss on chromosome 18q as a prognostic marker in stage II colorectal cancer. Gastroenterology. 1998;114:1180–7.

    Article  PubMed  CAS  Google Scholar 

  27. Jen J, Kim H, Piantadosi S, Liu ZF, Levitt RC, Sistonen P, 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 

  28. Ogunbiyi OA, Goodfellow PJ, Herfarth K, Gagliardi G, Swanson PE, Birnbaum EH, et al. Confirmation that chromosome 18q allelic loss in colon cancer is a prognostic indicator. J Clin Oncol. 1998;16:427–33.

    PubMed  CAS  Google Scholar 

  29. Carethers JM, Hawn MT, Greenson JK, Hitchcock CL, Boland CR. Prognostic significance of allelic lost at chromosome 18q21 for stage II colorectal cancer. Gastroenterology. 1998;114:1188–95.

    Article  PubMed  CAS  Google Scholar 

  30. Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature. 2000;408:307–10.

    Article  PubMed  CAS  Google Scholar 

  31. Lurje G, Zhang W, Lenz HJ. Molecular prognostic markers in locally advanced colon cancer. Clin Colorectal Cancer. 2007;6:683–90.

    Article  PubMed  CAS  Google Scholar 

  32. Munro AJ, Lain S, Lane DP. P53 abnormalities and outcomes in colorectal cancer: a systematic review. Br J Cancer. 2005;92:434–44.

    PubMed  CAS  Google Scholar 

  33. Iacopetta B, Russo A, Bazan V, Dardanoni G, Gebbia N, Soussi T, et al. Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study. Ann Oncol. 2006;17:842–7.

    Article  PubMed  CAS  Google Scholar 

  34. Andreyev HJ, Norman AR, Cunningham D, Oates JR, Clarke PA. Kirsten ras mutations in patients with colorectal cancer: the multicenter “RASCAL” study. J Natl Cancer Inst. 1998;90:675–84.

    Article  PubMed  CAS  Google Scholar 

  35. Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008;359:1757–65.

    Article  PubMed  CAS  Google Scholar 

  36. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, 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 

  37. Andreyev HJ, Norman AR, Cunningham D, Oates J, Dix BR, Iacopetta BJ, 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 

  38. Ogino S, Meyerhardt JA, Irahara N, Niedzwiecki D, Hollis D, Saltz LB, et al. KRAS mutation in stage III colon cancer and clinical outcome following intergroup trial CALGB 89803. Clin Cancer Res. 2009;15:7322–9.

    Article  PubMed  CAS  Google Scholar 

  39. Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu-Duvaz D, Good VM, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell. 2004;116:855–67.

    Article  PubMed  CAS  Google Scholar 

  40. Fransen K, Klintenas M, Osterstrom A, Dimberg J, Monstein HJ, Soderkvist P. Mutation analysis of the BRAF, ARAF and RAF-1 genes in human colorectal adenocarcinomas. Carcinogenesis. 2004;25:527–33.

    Article  PubMed  CAS  Google Scholar 

  41. Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, 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 

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

    Article  PubMed  CAS  Google Scholar 

  43. Ogino S, Nosho K, Kirkner GJ, Kawasaki T, Meyerhardt JA, Loda M, 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 

  44. French AJ, Sargent DJ, Burgart LJ, Foster NR, Kabat BF, Goldberg R, et al. Prognostic significance of defective mismatch repair and BRAF V600E in patients with colon cancer. Clin Cancer Res. 2008;14:3408–15.

    Article  PubMed  CAS  Google Scholar 

  45. Popat S, Matakidou A, Houlston RS. Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis. J Clin Oncol. 2004;22:529–36.

    Article  PubMed  CAS  Google Scholar 

  46. Allegra CJ, Paik S, Colangelo LH, Parr AL, Kirsch I, Kim G, et al. Prognostic value of thymidylate synthase, Ki-67, and p53 in patients with Dukes’ B and C colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project collaborative study. J Clin Oncol. 2003;21:241–50.

    Article  PubMed  CAS  Google Scholar 

  47. Ngan CY, Yamamoto H, Seshimo I, Ezumi K, Terayama M, Hemmi H, et al. A multivariate analysis of adhesion molecules expression in assessment of colorectal cancer. J Surg Oncol. 2007;95:652–62.

    Article  PubMed  CAS  Google Scholar 

  48. Kim J, Takeuchi H, Lam ST, Turner RR, Wang HJ, Kuo C, et al. Chemokine receptor CXCR4 expression in colorectal cancer patients increases the risk for recurrence and for poor survival. J Clin Oncol. 2005;23:2744–53.

    Article  PubMed  CAS  Google Scholar 

  49. Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299:425–36.

    Article  PubMed  CAS  Google Scholar 

  50. Schetter AJ, Nguyen GH, Bowman ED, Mathe EA, Yuen ST, Hawkes JE, et al. Association of inflammation-related and microRNA gene expression with cancer-specific mortality of colon adenocarcinoma. Clin Cancer Res. 2009;15:5878–87.

    Article  PubMed  CAS  Google Scholar 

  51. Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, et al. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol. 2011;29:610–8.

    Article  PubMed  Google Scholar 

  52. Pages F, Kirilovsky A, Mlecnik B, Asslaber M, Tosolini M, Bindea G, et al. In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J Clin Oncol. 2009;27:5944–51.

    Article  PubMed  CAS  Google Scholar 

  53. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313:1960–4.

    Article  PubMed  CAS  Google Scholar 

  54. Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med. 2005;353:2654–66.

    Article  PubMed  CAS  Google Scholar 

  55. Laghi L, Bianchi P, Miranda E, Balladore E, Pacetti V, Grizzi F, et al. CD3+ cells at the invasive margin of deeply invading (pT3-T4) colorectal cancer and risk of post-surgical metastasis: a longitudinal study. Lancet Oncol. 2009;10:877–84.

    Article  PubMed  CAS  Google Scholar 

  56. Noura S, Yamamoto H, Ohnishi T, Masuda N, Matsumoto T, Takayama O, et al. Comparative detection of lymph node micrometastases of stage II colorectal cancer by reverse transcriptase polymerase chain reaction and immunohistochemistry. J Clin Oncol. 2002;20:4232–41.

    Article  PubMed  CAS  Google Scholar 

  57. Ho SB, Hyslop A, Albrecht R, Jacobson A, Spencer M, Rothenberger DA, et al. Quantification of colorectal cancer micrometastases in lymph nodes by nested and real-time reverse transcriptase-PCR analysis for carcinoembryonic antigen. Clin Cancer Res. 2004;10:5777–84.

    Article  PubMed  CAS  Google Scholar 

  58. Liefers GJ, Cleton-Jansen AM, van de Velde CJ, Hermans J, van Krieken JH, Cornelisse CJ, et al. Micrometastases and survival in stage II colorectal cancer. N Engl J Med. 1998;339:223–8.

    Article  PubMed  CAS  Google Scholar 

  59. Bilchik AJ, Saha S, Wiese D, Stonecypher JA, Wood TF, Sostrin S, et al. Molecular staging of early colon cancer on the basis of sentinel node analysis: a multicenter phase II trial. J Clin Oncol. 2001;19:1128–36.

    PubMed  CAS  Google Scholar 

  60. Rosenberg R, Hoos A, Mueller J, Baier P, Stricker D, Werner M, et al. Prognostic significance of cytokeratin-20 reverse transcriptase polymerase chain reaction in lymph nodes of node-negative colorectal cancer patients. J Clin Oncol. 2002;20:1049–55.

    Article  PubMed  Google Scholar 

  61. Bernini A, Spencer M, Frizelle S, Madoff RD, Willmott LD, McCormick SR, et al. Evidence for colorectal cancer micrometastases using reverse transcriptase-polymerase chain reaction analysis of MUC2 in lymph nodes. Cancer Detect Prev. 2000;24:72–9.

    PubMed  CAS  Google Scholar 

  62. Harder J, Engelstaedter V, Usadel H, Lassmann S, Werner M, Baier P, et al. CpG-island methylation of the ER promoter in colorectal cancer: analysis of micrometastases in lymph nodes from UICC stage I and II patients. Br J Cancer. 2009;100:360–5.

    Article  PubMed  CAS  Google Scholar 

  63. Hayashi N, Ito I, Yanagisawa A, Kato Y, Nakamori S, Imaoka S, et al. Genetic diagnosis of lymph-node metastasis in colorectal cancer. Lancet. 1995;345:1257–9.

    Article  PubMed  CAS  Google Scholar 

  64. Sanchez-Cespedes M, Esteller M, Hibi K, Cope FO, Westra WH, Piantadosi S, et al. Molecular detection of neoplastic cells in lymph nodes of metastatic colorectal cancer patients predicts recurrence. Clin Cancer Res. 1999;5:2450–4.

    PubMed  CAS  Google Scholar 

  65. Waldman SA, Hyslop T, Schulz S, Barkun A, Nielsen K, Haaf J, et al. Association of GUCY2C expression in lymph nodes with time to recurrence and disease-free survival in pN0 colorectal cancer. JAMA. 2009;301:745–52.

    Article  PubMed  CAS  Google Scholar 

  66. Weitz J, Kienle P, Lacroix J, Willeke F, Benner A, Lehnert T, et al. Dissemination of tumor cells in patients undergoing surgery for colorectal cancer. Clin Cancer Res. 1998;4:343–8.

    PubMed  CAS  Google Scholar 

  67. Wharton RQ, Jonas SK, Glover C, Khan ZA, Klokouzas A, Quinn H, et al. Increased detection of circulating tumor cells in the blood of colorectal carcinoma patients using two reverse transcription-PCR assays and multiple blood samples. Clin Cancer Res. 1999;5:4158–63.

    PubMed  CAS  Google Scholar 

  68. Wong IH, Yeo W, Chan AT, Johnson PJ. Quantitative relationship of the circulating tumor burden assessed by reverse transcription-polymerase chain reaction for cytokeratin 19 mRNA in peripheral blood of colorectal cancer patients with Dukes’ stage, serum carcinoembryonic antigen level and tumor progression. Cancer Lett. 2001;162:65–73.

    Article  PubMed  CAS  Google Scholar 

  69. Uen YH, Lin SR, Wu DC, Su YC, Wu JY, Cheng TL, et al. Prognostic significance of multiple molecular markers for patients with stage II colorectal cancer undergoing curative resection. Ann Surg. 2007;246:1040–6.

    Article  PubMed  Google Scholar 

  70. Iinuma H, Watanabe T, Mimori K, Adachi M, Hayashi N, Tamura J, et al. Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with dukes’ stage B and C colorectal cancer. J Clin Oncol. 2011;29:1547–55.

    Article  PubMed  Google Scholar 

  71. Koch M, Kienle P, Kastrati D, Antolovic D, Schmidt J, Herfarth C, et al. Prognostic impact of hematogenous tumor cell dissemination in patients with stage II colorectal cancer. Int J Cancer. 2006;118:3072–7.

    Article  PubMed  CAS  Google Scholar 

  72. Gazzaniga P, Nofroni I, Gandini O, Silvestri I, Frati L, Agliano AM, et al. Tenascin C and epidermal growth factor receptor as markers of circulating tumoral cells in bladder and colon cancer. Oncol Rep. 2005;14:1199–202.

    PubMed  CAS  Google Scholar 

  73. Lecomte T, Berger A, Zinzindohoue F, Micard S, Landi B, Blons H, et al. Detection of free-circulating tumor-associated DNA in plasma of colorectal cancer patients and its association with prognosis. Int J Cancer. 2002;100:542–8.

    Article  PubMed  CAS  Google Scholar 

  74. Belluco C, Nitti D, Frantz M, Toppan P, Basso D, Plebani M, et al. Interleukin-6 blood level is associated with circulating carcinoembryonic antigen and prognosis in patients with colorectal cancer. Ann Surg Oncol. 2000;7:133–8.

    Article  PubMed  CAS  Google Scholar 

  75. Horie N, Aiba H, Oguro K, Hojo H, Takeishi K. Functional analysis and DNA polymorphism of the tandemly repeated sequences in the 5′-terminal regulatory region of the human gene for thymidylate synthase. Cell Struct Funct. 1995;20:191–7.

    Article  PubMed  CAS  Google Scholar 

  76. Kawakami K, Watanabe G. Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase gene. Cancer Res. 2003;63:6004–7.

    PubMed  CAS  Google Scholar 

  77. Mandola MV, Stoehlmacher J, Zhang W, Groshen S, Yu MC, Iqbal S, et al. A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels. Pharmacogenetics. 2004;14:319–27.

    Article  PubMed  CAS  Google Scholar 

  78. Lurje G, Zhang W, Yang D, Groshen S, Hendifar AE, Husain H, et al. Thymidylate synthase haplotype is associated with tumor recurrence in stage II and stage III colon cancer. Pharmacogenet Genomics. 2008;18:161–8.

    Article  PubMed  CAS  Google Scholar 

  79. Bandres E, Malumbres R, Cubedo E, Honorato B, Zarate R, Labarga A, et al. A gene signature of 8 genes could identify the risk of recurrence and progression in Dukes’ B colon cancer patients. Oncol Rep. 2007;17:1089–94.

    PubMed  CAS  Google Scholar 

  80. Wang Y, Jatkoe T, Zhang Y, Mutch MG, Talantov D, Jiang J, et al. Gene expression profiles and molecular markers to predict recurrence of Dukes’ B colon cancer. J Clin Oncol. 2004;22:1564–71.

    Article  PubMed  CAS  Google Scholar 

  81. Barrier A, Boelle PY, Roser F, Gregg J, Tse C, Brault D, et al. Stage II colon cancer prognosis prediction by tumor gene expression profiling. J Clin Oncol. 2006;24:4685–91.

    Article  PubMed  CAS  Google Scholar 

  82. Jiang Y, Casey G, Lavery IC, Zhang Y, Talantov D, Martin-McGreevy M, et al. Development of a clinically feasible molecular assay to predict recurrence of stage II colon cancer. J Mol Diagn. 2008;10:346–54.

    Article  PubMed  CAS  Google Scholar 

  83. Eschrich S, Yang I, Bloom G, Kwong KY, Boulware D, Cantor A, et al. Molecular staging for survival prediction of colorectal cancer patients. J Clin Oncol. 2005;23:3526–35.

    Article  PubMed  CAS  Google Scholar 

  84. Lin YH, Friederichs J, Black MA, Mages J, Rosenberg R, Guilford PJ, et al. Multiple gene expression classifiers from different array platforms predict poor prognosis of colorectal cancer. Clin Cancer Res. 2007;13:498–507.

    Article  PubMed  CAS  Google Scholar 

  85. Garman KS, Acharya CR, Edelman E, Grade M, Gaedcke J, Sud S, et al. A genomic approach to colon cancer risk stratification yields biologic insights into therapeutic opportunities. Proc Natl Acad Sci USA. 2008;105:19432–7.

    Article  PubMed  CAS  Google Scholar 

  86. Smith JJ, Deane NG, Wu F, Merchant NB, Zhang B, Jiang A, et al. Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer. Gastroenterology. 2010;138:958–68.

    Article  PubMed  CAS  Google Scholar 

  87. O’Connell MJ, Lavery I, Yothers G, Paik S, Clark-Langone KM, Lopatin M, et al. Relationship between tumor gene expression and recurrence in four independent studies of patients with stage II/III colon cancer treated with surgery alone or surgery plus adjuvant fluorouracil plus leucovorin. J Clin Oncol. 2010;28:3937–44.

    Article  PubMed  Google Scholar 

  88. Salazar R, Roepman P, Capella G, Moreno V, Simon I, Dreezen C, et al. Gene expression signature to improve prognosis prediction of stage II and III colorectal cancer. J Clin Oncol. 2011;29:17–24.

    Article  PubMed  Google Scholar 

  89. Gray R, Barnwell J, McConkey C, Hills RK, Williams NS, Kerr DJ. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 2007;370:2020–9.

    Article  PubMed  Google Scholar 

  90. PARSC study (NCT00903565). A prospective study for the assessment of recurrence risk in stage II colon cancer patients using ColoPrint (PARSC). http://clinicaltrials.gov/ct2/show/NCT00903565?term=parsc&rank=1.

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  1. Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

    Takashi Akiyoshi

  2. Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan

    Takashi Kobunai & Toshiaki Watanabe

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  1. Takashi Akiyoshi
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Akiyoshi, T., Kobunai, T. & Watanabe, T. Recent approaches to identifying biomarkers for high-risk stage II colon cancer. Surg Today 42, 1037–1045 (2012). https://doi.org/10.1007/s00595-012-0324-4

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