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KRAS mutation testing in therapeutic algorithm for treatment of metastatic colorectal carcinoma


Authors: Lenka Dubská 1;  Martina Vyskočilová 1;  Rudolf Nenutil 1;  Dalibor Valík 1;  Dana Knoflíčková 1;  Pavel Fabian 1;  Ilona Kocáková 1;  Regina Demlová 1;  Martin Beránek 2;  Monika Drastíková 2;  Hana Vošmiková 2;  Arpád Bóday 3;  Kateřina Horká 3;  Jarmila Šímová 4;  Jiří Drábek 5;  Jiří Ehrmann ml. 5;  Marián Hajdúch 5;  Milada Matějčková 6;  Radek Šíma 7;  Daniel Tvrdík 8;  Ctibor Povýšil 8;  Aleš Ryška 9
Authors‘ workplace: Masarykův onkologický ústav, Brno 1;  Univerzita Karlova v Praze, Lékařská fakulta Hradec Králové, Ústav klinické biochemie a diagnostiky FN 2;  P & R LAB a. s., Nový Jičín 3;  CGB laboratoř a. s., Ostrava 4;  Univerzila Palackého v Olomouci, Ústav molekulární a translační medicíny LF 5;  Fakultní Thomayerova nemocnice s poliklinikou v Praze, Oddělení patologie a molekulární medicíny 6;  Bioptická laboratoř s. r. o., Plzeň 7;  Univerzita Karlova v Praze, 1. lékařská fakulta, Ústav patologie VFN 8;  Univerzita Karlova v Praze, Lékařská fakulta Hradec Králové, Fingerlandův ústav patologie FN 9
Published in: Čas. Lék. čes. 2011; 150: 321-326
Category: Review Article

Overview

Targeted therapy has become an integral part of treatment procedures of malignant tumors. Colorectal carcinomas are frequently targeted with monoclonal anti-EGFR antibodies (cetuximab and panitumumab). Activating somatic mutations in codons 12 and 13 of the exon 2 of KRAS gene are considered negative predictive factors of response to anti-EGFR therapy in patients with metastatic colorectal cancer. In the Czech Republic, evaluation of mutational status of KRAS gene is performed in several referral laboratories. In 2009, these laboratories performed 2580 tests of the KRAS mutational status – out of these, 60.2% cases reported non-mutated, wild-type KRAS. In one of the referral laboratories, we demonstrate the logistics of KRAS testing procedure. Stratification of patients with metastatic colorectal tumors based on their KRAS mutational status has evolved to a standard procedure. Laboratories performing these methods shall therefore adhere to the recommendations of the professional and accredited societies.

Key words:
k-ras, colorectal carcinoma, targeted therapy, anti-EGFR therapy, predictive molecular oncology, standardization of diagnostic procedure.


Sources

1. Jasperson KW, et al. Hereditary and familial colon cancer. Gastroenterology 2010; 138: 2044–2058.

2. Vogelstein B, et al. Genetic alterations during colorectal-tumor development. N Engl J Med 1988; 319(9): 525–532.

3. Malumbres M, Barbacid M. RAS oncogenes: the first 30 years. Nat Rev Cancer 2003; 3(6): 459–465.

4. Carta C, et al. Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype. Am J Hum Genet 2006; 79(1): 129–135.

5. Karnoub AE, Weinberg RA. Ras oncogenes: split personalities. Nat Rev Mol Cell Biol 2008; 9(7): 517–531.

6. Bernards A, Settleman J. GEFs in growth factor signaling. Growth Factors 2007; 25(5): 355–361.

7. Scheffzek K, et al. The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science 1997; 277(5324): 333–338.

8. Krengel U, et al. Three-dimensional structures of H-ras p21 mutants: molecular basis for their inability to function as signal switch molecules. Cell 1990; 62(3): 539–548.

9. Ahmadian MR, et al. Confirmation of the arginine-finger hypothesis for the GAP-stimulated GTP-hydrolysis reaction of Ras. Nat Struct Biol 1997; 4(9): 686–689.

10. Moroni M, 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(5): 279–286.

11. Saltz LB, 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(7): 1201–1208.

12. Italiano A, et al. Cetuximab shows activity in colorectal cancer patients with tumors for which FISH analysis does not detect an increase in EGFR gene copy number. Ann Surg Oncol 2008; 15(2): 649–654.

13. Chung KY, 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(9): 1803–1810.

14. Bokemeyer C, et al. KRAS status and efficacy of first-line treatment of patients with metastatic colorectal cancer (mCRC) with FOLFOX with or without cetuximab: The OPUS experience (abstract 4000). J Clin Oncol 2008; 26: 4000.

15. Van Cutsem E, et al. KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: The CRYSTAL experience (abstract 2). J Clin Oncol 2008; 26: 2.

16. Lievre A, et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 2006; 66(8): 3992–3995.

17. Lievre A, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008; 26(3): 374–379.

18. Di Fiore F, et al. Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br J Cancer 2007; 96(8): 1166–1169.

19. Khambata-Ford S, et al. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 2007; 25(22): 3230–3237.

20. De Roock W, et al. KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 2008; 19(3): 508–515.

21. Allegra CJ, 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(12): 2091–2096.

22. Forbes SA, et al. COSMIC (the Catalogue of Somatic Mutations in Cancer): a resource to investigate acquired mutations in human cancer. Nucleic Acids Res 2010; 38 (Database issue): D652–657.

23. Loupakis F, 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(4): 715–721.

24. Lopez-Crapez E, et al. KRAS status analysis and anti-EGFR therapies: is comprehensiveness a biologist’s fancy or a clinical necessity? Br J Cancer 2010; 102(6): 1074–1075; author reply 1076–1077.

25. Smith G, et al. Activating K-Ras mutations outwith ‘hotspot’ codons in sporadic colorectal tumours - implications for personalised cancer medicine. Br J Cancer 2010; 102(4): 693–703.

26. Barbacid M. ras oncogenes: their role in neoplasia. Eur J Clin Invest 1990; 20(3): 225–235.

27. Davies H, et al. Mutations of the BRAF gene in human cancer. Nature 2002, 417(6892): 949–954.

28. Wan PT, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 2004; 116(6): 855–867.

29. Wellbrock C, et al. The RAF proteins take centre stage. Nat Rev Mol Cell Biol 2004; 5(11): 875–885.

30. Greer CE, et al. PCR amplification from paraffin-embedded tissues. Effects of fixative and fixation time. Am J Clin Pathol 1991; 95(2): 117–124.

31. Monzon FA, et al. The role of KRAS mutation testing in the management of patients with metastatic colorectal cancer. Arch Pathol Lab Med 2009; 133(10): 1600–1606.

32. van Krieken JHJM, et al. KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program. Virchows Archiv 2008; 453: 417–431.

33. ČSN EN ISO 15189:2007 (85 5101) Zdravotnické laboratoře – Zvláštní požadavky na kvalitu a způsobilost.

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