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Gastrointestinal and Pancreatobiliary Tumors

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Molecular Oncology Testing for Solid Tumors

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Abstract

Malignancies of the gastrointestinal tract have a high incidence and great impact on both cancer mortality and economic resources. Specifically colorectal cancer is the third most commonly diagnosed cancer in men and second in women throughout the world [1]. In 2012, there were over 1.2 million new cases of colorectal cancer and an estimated 608,700 deaths attributed to it worldwide. Both incidence and mortality have been slowly declining in the United States, but still account for nearly 10 % of all cancer deaths [2]. Elsewhere in the world, the incidence of colorectal cancer is on the rise, especially in Eastern Asia and Eastern Europe [3] (Fig. 12.1).

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–902.

    PubMed  Google Scholar 

  2. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9.

    PubMed  Google Scholar 

  3. Center MM, Jemal A, Ward E. International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev. 2009;18:1688.

    PubMed  Google Scholar 

  4. Ferlay J, Shin H, Bray F, et al. GLOBOCAN 2008: cancer incidence, mortality, and prevalence worldwide. Lyon: International Agency for Research on Cancer; 2010.

    Google Scholar 

  5. Lee BY, Sonnenberg A. Time trends of mortality from colorectal cancer in the United States: a birth-cohort analysis. JAMA. 2013;173:1148.

    Google Scholar 

  6. Ries L, Kosary CL, Hankey BF, et al. SEER cancer statistics review 1973–1995. Bethesda, MD: National Cancer Institute; 1998.

    Google Scholar 

  7. Center MM, Jemal A, Smith RA, Ward E. Worldwide variations in colorectal cancer. CA Cancer J Clin. 2009;59:366.

    PubMed  Google Scholar 

  8. Parkin DM. Epidemiology of cancer: global patterns and trends. Toxicol Lett. 1998;102–103:227.

    PubMed  Google Scholar 

  9. Pisani P, Parkin DM, Ferlay J. Estimates of the worldwide mortality from eighteen major cancers in 1985. Implications for prevention and projections of future burden. Int J Cancer. 1993;55:891.

    CAS  PubMed  Google Scholar 

  10. Anderson WFC, Fraumeni FJ, Rosenberg PS, Rabkin CS. Age-specific trends in incidence of noncardia gastric cancer in US adults. JAMA. 2010;303(17):1723.

    PubMed Central  CAS  PubMed  Google Scholar 

  11. Pohl H, Sirovich B, Welch HG. Esophageal adenocarcinoma incidence: are we reaching the peak? Cancer Epidemiol Biomarkers Prev. 2010;19:1468.

    PubMed  Google Scholar 

  12. Gholipour C, Shalchi RA, Abbasi M. A histopathological study of esophageal cancer on the western side of the Caspian littoral from 1994 to 2003. Dis Esophagus. 2008;21:322.

    CAS  PubMed  Google Scholar 

  13. Lagergren J, Bergström R, Lindgren A, Nyrén O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med. 1999;340:825.

    CAS  PubMed  Google Scholar 

  14. Lagergren J, Bergström R, Nyrén O. Association between body mass and adenocarcinoma of the esophagus and gastric cardia. Ann Intern Med. 1999;130:883.

    CAS  PubMed  Google Scholar 

  15. Heinemann V, Douillard JY, Ducreux M, Peeters M. Targeted therapy in metastatic colorectal cancer – an example of personalised medicine in action. Cancer Treat Rev. 2013;39(6):592–601.

    CAS  PubMed  Google Scholar 

  16. Kopetz S, Chang GJ, Overman MJ, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009;27:3677–83.

    PubMed Central  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  18. Garrett TP, McKern NM, Lou M, Elleman TC, Adams TE, Lovrecz GO, et al. The crystal structure of a truncated ErbB2 ectodomain reveals an active confirmation, poised to interact with other ErbB2 receptors. Mol Cell. 2003;11:495–505.

    CAS  PubMed  Google Scholar 

  19. Holbro T, Beerli RR, Maurer F, Koziczak M, Barbas 3rd CF, Hynes NE. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc Natl Acad Sci U S A. 2003;100:8933–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  20. Ajani JA, Bentrem DJ, Besh S, D’Amico TA, Das P, Denlinger C, et al. Gastric cancer, version 2.2013: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2013;11(5):531–46.

    CAS  PubMed  Google Scholar 

  21. Boku N. HER2-positive gastric cancer. Gastric Cancer. 2014;17:1–12.

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Gomez-Martin C, Plaza JC, Pazo-Cid R, Salud A, Pons F, Fonseca P, et al. Level of HER2 gene amplification predicts response and overall survival in HER2-positive advanced gastric cancer treated with trastuzumab. J Clin Oncol. 2013;31:4445–52.

    CAS  PubMed  Google Scholar 

  23. Van Cutsem E, Kang Y, Chung H, et al. Efficacy results from the TOGA trial: a phase III study of trastuzumab added to standard chemotherapy in first line human epidermal growth factor receptor 2 (HER2) positive advanced gastric cancer. J Clin Oncol. 2009;27(18s):4509.

    Google Scholar 

  24. Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52:797–805.

    CAS  PubMed  Google Scholar 

  25. Bang YJ, Van Cutsem E, Feyerislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomized controlled trial. Lancet. 2010;376:687–97.

    CAS  PubMed  Google Scholar 

  26. Yan M, Parker BA, Schwab R, Kurzrock R. HER2 aberrations in cancer: implications for therapy. Cancer Treat Rev. 2014;40(6):770–80.

    CAS  PubMed  Google Scholar 

  27. Kushima R, Kuwata T, Yao T, Kuriki H, Hashizume K, Masuda S, et al. Interpretation of HER2 tests in gastric cancer: confirmation of interobserver differences and validation of a QA/QC educational program. Virchows Arch. 2014;464(5):539–45.

    CAS  PubMed  Google Scholar 

  28. Ruschoff J, Hanna W, Bilous M, Hofmann M, Osamura RY, Penault-Llorca F, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol. 2012;25(5):637–50.

    PubMed  Google Scholar 

  29. Ruschoff J, Dietel M, Beretton G, et al. HER2 diagnostics in gastric cancer: guideline validation and development of standardized immunohistochemicl testing. Virchows Arch. 2010;457(3):299–307.

    PubMed Central  PubMed  Google Scholar 

  30. Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25:118–45.

    CAS  PubMed  Google Scholar 

  31. Albarello L, Pecciarini L, Doglioni C. HER2 testing in gastric cancer. Adv Anat Pathol. 2011;18(1):53–9. PMID: 21169738.

    CAS  PubMed  Google Scholar 

  32. Chen M, Li Y, Ming Z, Biao A, Zheng LX. Comparison of HER2 status by fluorescence in situ hydridisation and immunohistochemistry in gastric cancer. Contemp Oncol (Pozn). 2014;18(2):95–9.

    Google Scholar 

  33. de la Chapelle A. Microsatellite instability. N Engl J Med. 2003;349:209.

    PubMed  Google Scholar 

  34. Gruber SB. New developments in Lynch syndrome (hereditary nonpolyposis colorectal cancer) and mismatch repair gene testing. Gastroenterology. 2006;130:577.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  36. Thibodeau SN, French AJ, Cunningham JM, et al. Microsatellite instability in colorectal cancer: different mutator phenotypes and the principal involvement of hMLH1. Cancer Res. 1998;58:1713.

    CAS  PubMed  Google Scholar 

  37. 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.

    PubMed Central  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  39. Aaltonen LA, Peltomäki P, Mecklin JP, et al. Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients. Cancer Res. 1994;54:1645–8.

    CAS  PubMed  Google Scholar 

  40. 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.

    PubMed Central  CAS  PubMed  Google Scholar 

  41. 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.

    PubMed Central  CAS  PubMed  Google Scholar 

  42. Bertagnolli MM, Niedzwiecki D, Compton CC, et al. 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. 2009;27:1814–21.

    PubMed Central  CAS  PubMed  Google Scholar 

  43. Musulen E, Sanz C, Munoz-Marmol AM, Ariza A. Mismatch repair protein immunohistochemistry: a useful population screening strategy for Lynch syndrome. Hum Pathol. 2014;45(7):1388–96.

    CAS  PubMed  Google Scholar 

  44. 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;24:241–51.

    CAS  PubMed  Google Scholar 

  45. Murphy KM, Zhang S, Geiger T, et al. Comparison of the microsatellite instability analysis system and the Bethesda panel for the determination of microsatellite instability in colorectal cancers. J Mol Diagn. 2006;8(3):305–11.

    PubMed Central  CAS  PubMed  Google Scholar 

  46. 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;99(3):244–52.

    CAS  PubMed  Google Scholar 

  47. 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.

    CAS  PubMed  Google Scholar 

  48. Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96(4):261–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  49. Pagin A, Zerimech F, Leclerc J, Wacrenier A, Lejeune S, Descarpentries C, 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):2079–87.

    PubMed Central  CAS  PubMed  Google Scholar 

  50. de la Chapelle A, Hampel H. Clinical relevance of microsatellite instability in colorectal cancer. J Clin Oncol. 2010;28(20):3380–7.

    PubMed Central  PubMed  Google Scholar 

  51. Ciardiello F, Tortora G. A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res. 2001;7:2958.

    CAS  PubMed  Google Scholar 

  52. Real FX, Rettig WJ, Chesa PG, et al. Expression of epidermal growth factor receptor in human cultured cells and tissues: relationship to cell lineage and stage of differentiation. Cancer Res. 1986;46:4726.

    CAS  PubMed  Google Scholar 

  53. Scaltriti M, Baselga J. The epidermal growth factor receptor pathway: a model for targeted therapy. Clin Cancer Res. 2006;12(18):5268–72.

    CAS  PubMed  Google Scholar 

  54. Mitsudomi T, Yatabe Y. Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS J. 2010;277(2):301–8.

    CAS  PubMed  Google Scholar 

  55. Personeni N, Fieuws S, Piessevaux H, et al. Clinical usefulness of EGFR gene copy number as a predictive marker in colorectal cancer patients treated with cetuximab: a fluorescent in situ hybridization study. Clin Cancer Res. 2008;14:5869–76.

    CAS  PubMed  Google Scholar 

  56. Hecht JR, Mitchell E, Neubauer MA, et al. Lack of correlation between epidermal growth factor receptor status and response to panitumumab monotherapy in metastatic colorectal cancer. Clin Cancer Res. 2010;16(7):2205–13.

    CAS  PubMed  Google Scholar 

  57. Siena S, Sartore-Bianchi A, Di Nicolantoni F, Balfour J, Bardelli A. Biomarkers predicting clinical outcome of epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer. J Natl Cancer Inst. 2009;101(19):1308–24.

    PubMed Central  CAS  PubMed  Google Scholar 

  58. Shia J, Klimstra DS, Li AR, et al. Epidermal growth factor receptor expression and gene amplification in colorectal carcinoma: an immunohistochemical and chromogenic in situ hybridization study. Mod Pathol. 2005;18(10):1350–6.

    CAS  PubMed  Google Scholar 

  59. Ooi A, Takehana T, Li X, et al. Protein overexpression and gene amplification of HER-2 and EGFR in colorectal cancers: an immunohistochemical and fluorescent in situ hybridization study. Mod Pathol. 2004;17(8):895–904.

    CAS  PubMed  Google Scholar 

  60. Sartore-Bianchi A, Moroni M, Veronese S, et al. Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab. J Clin Oncol. 2007;25(22):3238–45.

    CAS  PubMed  Google Scholar 

  61. Bos JL, Fearon ER, Hamilton SE, et al. Prevelance of ras gene mutations in human colorectal cancers. Nature. 1987;327:293.

    CAS  PubMed  Google Scholar 

  62. Downward J. Targeting RAS, signaling pathways in cancer therapy. Nat Rev Cancer. 2003;3:11.

    CAS  PubMed  Google Scholar 

  63. Gupta S, Ramjaun AR, Haiko P, et al. Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice. Cell. 2007;129:957.

    CAS  PubMed  Google Scholar 

  64. 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.

    CAS  PubMed  Google Scholar 

  65. 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.

    CAS  PubMed  Google Scholar 

  66. Dahabreh IJ, Terasawa T, Castaldi PJ, Trikalinos TA. Systematic review: anti-epidermal growth factor receptor treatment effect modification by KRAS mutations in advanced colorectal cancer. Ann Intern Med. 2011;154(1):37–49.

    PubMed  Google Scholar 

  67. Allegra CJ, Jessup JM, Somerfield MR, et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 2009;27:2091.

    PubMed  Google Scholar 

  68. Bristol-Myers Squibb Company. Erbitux (cetuximab) [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2012.

    Google Scholar 

  69. Amgen Inc. Vectibix (panatumumab) [package insert]. Thousand Oaks, CA: Amgen Inc; 2012.

    Google Scholar 

  70. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–45.

    CAS  PubMed  Google Scholar 

  71. Monzon FA, Ogino S, Hammond ME, Halling KC, Bloom KJ, Nikiforova MN. The role of KRAS mutation testing in the management of patients with metastatic colorectal cancer. Arch Pathol Lab Med. 2009;133(10):1600–6.

    CAS  PubMed  Google Scholar 

  72. Lievre A, Bachatte J-B, Blige V, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with Cetuximab. J Clin Oncol. 2008;26:374–9.

    CAS  PubMed  Google Scholar 

  73. Rodriguez R. Biomarker testing for treatment of metastatic colorectal cancer: role of the pathologist in community practice. J Community Support Oncol. 2014;12(1):27–32.

    CAS  PubMed  Google Scholar 

  74. Franklin WA, Haney J, Sugita M, Bemis L, Jimeno A, Messersmith WA. KRAS mutation: comparison of testing methods and tissue sampling techniques in colon cancer. J Mol Diagn. 2010;12:43–50.

    PubMed Central  CAS  PubMed  Google Scholar 

  75. Etienne-Gimeldi M-C, Formenta J-L, Francoual M, et al. KRAS mutations in treatment outcome in colorectal cancer in patients receiving exclusive fluoropyrimidine. Clin Cancer Res. 2008;14:4830–5.

    Google Scholar 

  76. Wang HL, Lopategui J, Amin MB, Patterson SD. KRAS mutation testing in human cancers: the pathologist’s role in the era of personalized medicine. Adv Anat Pathol. 2010;17(1):23–32.

    CAS  PubMed  Google Scholar 

  77. Ross JS. Clinical implementation of KRAS testing in metastatic colorectal carcinoma: the pathologist’s perspective. Arch Pathol Lab Med. 2012;136(10):1298–307.

    CAS  PubMed  Google Scholar 

  78. Bellon E, Ligtenberg MJ, Tejpar S, et al. External quality assessment for KRAS testing is needed: setup of a European program and report of the first joined regional quality assessment rounds. Oncologist. 2011;16:467–78.

    PubMed Central  CAS  PubMed  Google Scholar 

  79. 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. 2010;304:1812–20.

    PubMed  Google Scholar 

  80. Wong N, Gonazalez D, Salto-Teliez M, Butler R, Diaz-Cano SJ, Ilyas M, et al. RAS testing of colorectal carcinoma-a guidance document from the Association of Clinical Pathologists Molecualr Pathology and Diagnostics Group. J Clin Pathol. 2014;67:751–7.

    PubMed  Google Scholar 

  81. Kothari N, Schell MJ, Teer JK, Yeatman T, Shibata D, Kim R. Comparison of KRAS mutational analysis of colorectal cancer samples by standard testing and next-generation sequencing. J Clin Pathol. 2014. doi:10.1136/jclinpath-2014-202405.

    PubMed  Google Scholar 

  82. Douillard JY, Oliner KS, Siena S, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013;369:1023–34.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  85. Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene. 2007;26(22):3279–90.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  87. Tie J, Desai J. Targeting BRAF mutant metastatic colorectal cancer: clinical implications and emerging therapeutic strategies. Target Oncol. 2014. doi:10.1007/s11523-014-0330-0.

    PubMed Central  Google Scholar 

  88. Neumann J, Wehweck L, Maatz S, Engel J, Kirchner T, Jung A. Alterations in the EGFR pathway coincide in colorectal cancer and impact on prognosis. Virchows Arch. 2013;463(4):509–23.

    CAS  PubMed  Google Scholar 

  89. Lopez-Rios F, Angulo B, Gomez B, Mair D, Martinez R, Conde E, et al. Comparison of testing methods for the detection of BRAF V600E mutations in malignant melanoma: pre-approval validation study of the comparison diagnostic test for vemurafenib. PLoS One. 2013;8(1), e53733.

    PubMed Central  CAS  PubMed  Google Scholar 

  90. Curry JL, Torres-Cabala CA, Tetzlaff MT, et al. Molecular platforms utilized to detect BRAF V600E mutation in melanoma. Semin Cutan Med Surg. 2012;31:267–73.

    CAS  PubMed  Google Scholar 

  91. Hindson BJ, Ness KD, Masquelier DA, et al. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal Chem. 2011;83:8604–10.

    PubMed Central  CAS  PubMed  Google Scholar 

  92. Capper D, Preusser M, Habel A, et al. Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. Acta Neuropathol. 2011;122:11–9.

    CAS  PubMed  Google Scholar 

  93. Lasota J, Kowalik A, Wasag B, Wang ZF, Fellisiak-Golabek A, Coates T, et al. Detection of the BRAF V600E mutation in colon carcinoma: critical evaluation of the imunohistochemical approach. Am J Surg Pathol. 2014;38(9):1235–41.

    PubMed  Google Scholar 

  94. Souglakos J, Philips J, Wang R, et al. Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer. 2009;101:465.

    PubMed Central  CAS  PubMed  Google Scholar 

  95. Samowitz WS, Sweeney C, Herrick J, Albertsen H, Levin TR, Murtaugh MA, et al. Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res. 2005;65(14):6063–9.

    CAS  PubMed  Google Scholar 

  96. Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, et al. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012;48(10):1466–75.

    CAS  PubMed  Google Scholar 

  97. Nishihara R, Lochhead P, Kuchiba A, Jung S, Yamauchi M, Liao X, et al. Aspirin use and risk of colorectal cancer according to BRAF mutation status. JAMA. 2013;309(24):2563–71.

    PubMed Central  CAS  PubMed  Google Scholar 

  98. Cantwell-Dorris ER, O’Leary JJ, Sheils OM. BRAFV600E: implications for carcinogenesis and molecular therapy. Mol Cancer Ther. 2011;10:385–94.

    CAS  PubMed  Google Scholar 

  99. Hertzman Johansson C, Brage Egyhazi S. BRAF inhibitors in cancer therapy. Pharmcol Ther. 2014;142(2):176–82.

    CAS  Google Scholar 

  100. Tie J, Gibbs P, Lipton L, Christie M, Jorissen RN, Burgess AW, et al. Optimizing targeted therapeutic development: analysis of a colorectal cancer patient population with the BRAF(V600E) mutation. Int J Cancer. 2011;128(9):2075–84.

    CAS  PubMed  Google Scholar 

  101. Kopetz S, Desai J, Chan E, Hecht JR, O’Dwyer PJ, Lee RJ, et al. PLX4032 in metastatic colorectal cancer patients with mutant BRAF tumors. J Clin Oncol. 2010;28(15):3534.

    Google Scholar 

  102. Shaib W, Mahajan R, El-Rayes B. Markers of resistance to anti-EGFR therapy in colorectal cancer. J Gastrointest Oncol. 2013;4:308–18.

    PubMed Central  CAS  PubMed  Google Scholar 

  103. Samuels Y, Wang Z, Bardelli A, et al. High frequency of mutations of the PI3KCA gene in human cancers. Science. 2004;305:554.

    Google Scholar 

  104. 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.

    CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  106. Sartore-Bianchi A, Martini M, Molinari F, et al. PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res. 2009;69:1851–7.

    CAS  PubMed  Google Scholar 

  107. Prenen H, De Schutter J, Jacobs B, et al. PIK3CA mutations are not a major determinant of resistance to the epidermal growth factor receptor inhibitor cetuximab in metastatic colorectal cancer. Clin Cancer Res. 2009;15:3184–8.

    CAS  PubMed  Google Scholar 

  108. Huang L, Liu Z, Deng D, Tan A, Liao M, Mo Z, et al. Anti-epidermal growth factor receptor monoclonal antibody-based therapy for metastatic colorectal cancer: a meta-analysis of the effect of PIK3CA mutations in KRAS wild-type patients. Arch Med Sci. 2014;10(1):1–9.

    PubMed Central  PubMed  Google Scholar 

  109. Yuan TL, Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene. 2008;27(41):5497–510.

    PubMed Central  CAS  PubMed  Google Scholar 

  110. Liao X, Lockhead P, Nishihara R, Morikawa T, Kuchiba A, Yamauchi M, et al. Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. N Engl J Med. 2012;367(17):1596–606.

    PubMed Central  CAS  PubMed  Google Scholar 

  111. Ogino S, Liao X, Imamura Y, Yamauchi M, McCLeary NJ, Ng K, et al. Predictive and prognostic analysis of PIK3CA mutation in stage III colon cancer intergroup trial. J Natl Cancer Inst. 2013;105(23):1789–98.

    PubMed Central  CAS  PubMed  Google Scholar 

  112. Fadhil W, Ibrahem S, Seth R, Ilyas M. Quick-multiplex-consensus (QMC)-PCR followed by high-resolution melting: a simple and robust method for mutation detection in formalin-fixed paraffin-embedded tissue. J Clin Pathol. 2010;63:134–40.

    CAS  PubMed  Google Scholar 

  113. Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature. 1993;362:841–4.

    CAS  PubMed  Google Scholar 

  114. Zachary I. Signaling mechanisms mediating vascular protective actions of vascular endothelial growth factor. Am J Physiol Cell Physiol. 2001;280:C1375–86.

    CAS  PubMed  Google Scholar 

  115. Ferrara N, Hillan KJ, Gerber HP, et al. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 2004;3:391–400.

    CAS  PubMed  Google Scholar 

  116. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.

    CAS  PubMed  Google Scholar 

  117. Hochster HS, Hart LL, Ramanathan RK, et al. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE study. J Clin Oncol. 2008;26:3523–9.

    CAS  PubMed  Google Scholar 

  118. Ohtsu A, Shah MA, Van Cutsem E, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011;29:3968–76.

    CAS  PubMed  Google Scholar 

  119. Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-esophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31–9.

    CAS  PubMed  Google Scholar 

  120. Bang YJ, Kang YK, Kang WK, et al. Phase II study of sunitinib as second-line treatment for advanced gastric cancer. Invest New Drugs. 2011;29:1449–58.

    PubMed Central  CAS  PubMed  Google Scholar 

  121. Ilson D, Janjigian YY, Shah MA, et al. Phase II trial of sorafenib in esophageal (E) and gastroesophageal junction (GEJ) cancer: response and protracted stable disease observed in adenocarcinoma. J Clin Oncol. 2011;29:Abstract 4100.

    Google Scholar 

  122. Reichert JM. Antibody-based therapeutics to watch in 2011. MAbs. 2011;3:76–99.

    PubMed Central  PubMed  Google Scholar 

  123. Chung C, Pherwani N. Ziv-aflibercept: a novel angiogenesis inhibitor for the treatment of metastatic colorectal cancer. Am J Health Syst Pharm. 2013;70(21):1887–96.

    CAS  PubMed  Google Scholar 

  124. Hecht JR, Mitchell E, Chidiac T, et al. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol. 2009;27:672–80.

    CAS  PubMed  Google Scholar 

  125. Tol J, Koopman M, Cats A, et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med. 2009;360:563–72.

    CAS  PubMed  Google Scholar 

  126. Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouché O, Mineur L, Barone C, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381:303–12.

    CAS  PubMed  Google Scholar 

  127. Wilhelm SM, Dumas J, Adnane L, Lynch M, Carter CA, Schütz G, Thierauch KH, Zopf D. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer. 2011;129:245–55.

    CAS  PubMed  Google Scholar 

  128. Vallböhmer D, Zhang W, Gordon M, et al. Molecular determinants of cetuximab efficacy. J Clin Oncol. 2005;23(15):3536–44.

    PubMed  Google Scholar 

  129. Hayashi H, Arao T, Matsumoto K, Kimura H, Togashi Y, Hirashima Y, et al. Biomarkers of reactive resistance and early disease progression during chemotherapy during bevacizumab treatment for colorectal carcinom. Oncotarget. 2014;5(9):2588–95.

    PubMed Central  PubMed  Google Scholar 

  130. Lieu C, Tran H, Jiang ZQ, Mao M, Overman MJ, Lin E, et al. The association of alternate VEGF ligands with resistance to anti-VEGF therapy in metastatic colorectal cancer. PLoS One. 2013;8(10), e77117.

    PubMed Central  CAS  PubMed  Google Scholar 

  131. Andreozzi M, Quagliata L, Gsponer JR, Ruiz C, Vuaroqueaux V, EppenbergerCastori S, et al. VEGFA gene locus analysis across 80 human tumour types reveals gene amplification in several neoplastic entities. Angiogenesis. 2014;17(3):519–27.

    CAS  PubMed  Google Scholar 

  132. Watanabe K, Hasegawa Y, Yamashita H, Shimizu K, Ding Y, Abe M, et al. Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis. J Clin Invest. 2004;114:898.

    PubMed Central  CAS  PubMed  Google Scholar 

  133. Yan Y, Shen Z, Ye Y, Jiang K, Zhang H, Shen C, et al. A novel molecular marker of prognosis in colorectal cancer: vasohibin-1. Med Oncol. 2014;31(2):816.

    PubMed  Google Scholar 

  134. Gray RG, Quirke P, Handley K, et al. Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer. J Clin Oncol. 2011;29(35):4611–9.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  136. Kennedy RD, Bylesjo M, Kerr P, et al. Development and independent validation of a prognostic assay for stage II colon cancer using formalin-fixed paraffin-embedded tissue. J Clin Oncol. 2011;29(35):4620–6.

    PubMed  Google Scholar 

  137. Benson 3rd AB, Schrag D, Somerfield MR, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22:3408.

    PubMed  Google Scholar 

  138. Deeb KK, Sram JP, Gao H, Fakih MG. Multigene assays in metastatic colorectal cancer. J Natl Compr Canc Netw. 2013;11 Suppl 4:9–17.

    Google Scholar 

  139. Shirota Y, Stoehlmacher J, Brabender J, et al. ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol. 2001;19:4298–304.

    CAS  PubMed  Google Scholar 

  140. Krumbach R, Schuler J, Hofmann M, et al. Primary resistance to cetuximab in a panel of patient-derived tumour xenograft models: activation of MET as one mechanism for drug resistance. Eur J Cancer. 2011;47:1231–43.

    CAS  PubMed  Google Scholar 

  141. Metzker ML. Sequencing technologies – the next generation. Nat Rev Genet. 2010;11(1):31–46.

    CAS  PubMed  Google Scholar 

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Acknowledgement

The authors would like to acknowledge Ms. Lindsey Diamond for her assistance in the submission of this chapter.

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  1. Department of Internal Medicine, Virginia Commonwealth University Medical Center, 1201 East Marshall Street, 11th Floor, Room 11-212, Richmond, VA, 23298, USA

    Khalid Matin M.D., F.A.C.P. & Sarah W. Gordon M.D.

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  1. Khalid Matin M.D., F.A.C.P.
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  2. Sarah W. Gordon M.D.
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Correspondence to Khalid Matin M.D., F.A.C.P. .

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  1. Department of Pathology, Virginia Commonwealth University, Richmond, Virginia, USA

    Michael Ola Idowu

  2. Department of Pathology, Virginia Commonwealth University, Richmond, Virginia, USA

    Catherine Isabelle Dumur

  3. Department of Pathology, Virginia Commonwealth University, Richmond, Virginia, USA

    Carleton Theodore Garrett

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Matin, K., Gordon, S.W. (2015). Gastrointestinal and Pancreatobiliary Tumors. In: Idowu, M., Dumur, C., Garrett, C. (eds) Molecular Oncology Testing for Solid Tumors. Springer, Cham. https://doi.org/10.1007/978-3-319-16304-8_12

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  • DOI: https://doi.org/10.1007/978-3-319-16304-8_12

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