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International Journal of Colorectal Disease

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04.06.2018 | Original Article

Clinical significance of the BRAFV600E mutation in Asian patients with colorectal cancer

verfasst von: Hou-Hsuan Cheng, Jen-Kou Lin, Wei-Shone Chen, Jeng-Kai Jiang, Shung-Haur Yang, Shih-Ching Chang

Erschienen in: International Journal of Colorectal Disease | Ausgabe 9/2018

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Abstract

Background

To investigate the clinicopathological features and prognostic significance of the BRAFV600E mutation in Asian patients with colorectal cancer.

Methods

We retrospectively reviewed the medical records of 1969 patients with colorectal cancer admitted to Taipei Veterans General Hospital for surgical treatment between 2000 and 2013. The measured endpoint was overall survival after surgery. The prognostic value of the BRAFV600E mutation was analyzed using the log-rank test and Cox regression analysis.

Results

The BRAFV600E mutation was detected in 106 (5.4%) patients and associated with female gender, abnormal cancer antigen (CA)19-9 at diagnosis, microsatellite status, right-sided primary tumors, mucinous histology, poor differentiation, and lymphovascular invasion. Metastatic patterns were more common in non-regional lymph node metastasis (20.8 vs. 7.4%, p = 0.06) and peritoneal seeding (41. vs. 21.2%, p = 0.04). Mutations were not prognostic in the overall survival of the entire study group but only in specific patients: age < 65, normal carcinoembryonic antigen at diagnosis, and stage IV disease.

Conclusion

The BRAFV600E mutation was associated with distinct clinicopathological features and metastatic patterns. The overall survival rate was lower in selected colorectal patients with the BRAFV600E mutation.

Ministry of Health and Welfare (2016) Taiwan Cancer Registry annual report, 2013. In: Ministry of Health and Welfare

Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767CrossRefPubMed

Morin PJ, Sparks AB, Korinek V et al (1997) Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275:1787–1790CrossRefPubMed

Joo M, Shahsafaei A, Odze RD (2009) Paneth cell differentiation in colonic epithelial neoplasms: evidence for the role of the Apc/beta-catenin/Tcf pathway. Hum Pathol 40:872–880. https://doi.org/10.1016/j.humpath.2008.12.003 CrossRefPubMed

Huang CS, O’Brien MJ, Yang S, Farraye FA (2004) Hyperplastic polyps, serrated adenomas, and the serrated polyp neoplasia pathway. Am J Gastroenterol 99:2242–2255. https://doi.org/10.1111/j.1572-0241.2004.40131.x CrossRefPubMed

O’Brien MJ, Yang S, Mack C et al (2006) Comparison of microsatellite instability, CpG island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distinct colorectal carcinoma end points. Am J Surg Pathol [Internet] 30(12):1491–1501CrossRef

Leggett B, Whitehall V (2010) Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology 138:2088–2100. https://doi.org/10.1053/j.gastro.2009.12.066 CrossRefPubMed

Chong H, Vikis HG, Guan KL (2003) Mechanisms of regulating the RAF kinase family. Cell Signal 15:463–469CrossRefPubMed

Lito P, Rosen N, Solit DB (2013) Tumor adaptation and resistance to RAF inhibitors. Nat Med 19:1401–1409. https://doi.org/10.1038/nm.3392 CrossRefPubMed

10.

Sclafani F, Gullo G, Sheahan K, Crown J (2013) BRAF mutations in melanoma and colorectal cancer: a single oncogenic mutation with different tumour phenotypes and clinical implications. Crit Rev Oncol Hematol 87:55–68. https://doi.org/10.1016/j.critrevonc.2012.11.003 CrossRefPubMed

11.

Pratilas CA, Taylor BS, Ye Q et al (2009) (V600E)BRAF is associated with disabled feedback inhibition of RAF-MEK signaling and elevated transcriptional output of the pathway. Proc Natl Acad Sci U S A 106:4519–4524. https://doi.org/10.1073/pnas.0900780106 CrossRefPubMedPubMedCentral

12.

Pakneshan S, Salajegheh A, Smith RA, AK-Y L (2013) Clinicopathological relevance of BRAF mutations in human cancer. Pathology (Phila) 45:346–356. https://doi.org/10.1097/PAT.0b013e328360b61d CrossRef

13.

Toon CW, Walsh MD, Chou A et al (2013) BRAFV600E immunohistochemistry facilitates universal screening of colorectal cancers for Lynch syndrome. Am J Surg Pathol 37:1592–1602. https://doi.org/10.1097/PAS.0b013e31828f233d CrossRefPubMedPubMedCentral

14.

Thiel A, Heinonen M, Kantonen J et al (2013) BRAF mutation in sporadic colorectal cancer and lynch syndrome. Virchows Arch Int J Pathol 463:613–621. https://doi.org/10.1007/s00428-013-1470-9. CrossRef

15.

Samowitz WS, Sweeney C, Herrick J et al (2005) Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res 65:6063–6069. https://doi.org/10.1158/0008-5472.CAN-05-0404 CrossRefPubMed

16.

Zlobec I, Bihl MP, Schwarb H et al (2010) Clinicopathological and protein characterization of BRAF- and K-RAS-mutated colorectal cancer and implications for prognosis. Int J Cancer 127:367–380. https://doi.org/10.1002/ijc.25042. CrossRefPubMed

17.

Roth AD, Tejpar S, Delorenzi M et al (2010) 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 Off J Am Soc Clin Oncol 28:466–474. https://doi.org/10.1200/JCO.2009.23.3452 CrossRef

18.

Fariña-Sarasqueta A, van Lijnschoten G, Moerland E et al (2010) The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients. Ann Oncol Off J Eur Soc Med Oncol 21:2396–2402. https://doi.org/10.1093/annonc/mdq258 CrossRef

19.

Pai RK, Jayachandran P, Koong AC et al (2012) BRAF-mutated, microsatellite-stable adenocarcinoma of the proximal colon: an aggressive adenocarcinoma with poor survival, mucinous differentiation, and adverse morphologic features. Am J Surg Pathol 36:744–752. https://doi.org/10.1097/PAS.0b013e31824430d7 CrossRefPubMed

20.

Kalady MF, Dejulius KL, Sanchez JA et al (2012) BRAF mutations in colorectal cancer are associated with distinct clinical characteristics and worse prognosis. Dis Colon Rectum 55:128–133. https://doi.org/10.1097/DCR.0b013e31823c08b3 CrossRefPubMed

21.

Sinicrope FA, Mahoney MR, Smyrk TC, Thibodeau SN, Warren RS, Bertagnolli MM, Nelson GD, Goldberg RM, Sargent DJ, Alberts SR (2013) Prognostic impact of deficient DNA mismatch repair in patients with stage iii colon cancer from a randomized trial of FOLFOX-based adjuvant chemotherapy. J Clin Oncol 31:3664–3672. https://doi.org/10.1200/JCO.2013.48.9591 CrossRefPubMedPubMedCentral

22.

Yokota T, Ura T, Shibata N, Takahari D, Shitara K, Nomura M, Kondo C, Mizota A, Utsunomiya S, Muro K, Yatabe Y (2011) BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer. Br J Cancer 104:856–862. https://doi.org/10.1038/bjc.2011.19 CrossRefPubMedPubMedCentral

23.

Modest DP, Ricard I, Heinemann V, Hegewisch-Becker S, Schmiegel W, Porschen R, Stintzing S, Graeven U, Arnold D, von Weikersthal LF, Giessen-Jung C, Stahler A, Schmoll HJ, Jung A, Kirchner T, Tannapfel A, Reinacher-Schick A (2016) Outcome according to KRAS-, NRAS- and BRAF-mutation as well as KRAS mutation variants: pooled analysis of five randomized trials in metastatic colorectal cancer by the AIO colorectal cancer study group. Ann Oncol 27:1746–1753. https://doi.org/10.1093/annonc/mdw261 CrossRefPubMedPubMedCentral

24.

Gonsalves WI, Mahoney MR, Sargent DJ, Nelson GD, Alberts SR, Sinicrope FA, Goldberg RM, Limburg PJ, Thibodeau SN, Grothey A, Hubbard JM, Chan E, Nair S, Berenberg JL, McWilliams R, Alliance for Clinical Trials in Oncology (2014) Patient and tumor characteristics and BRAF and KRAS mutations in colon cancer, NCCTG/Alliance N0147. JNCI: J Natl Cancer Inst 106. https://doi.org/10.1093/jnci/dju106

25.

Price TJ, Hardingham JE, Lee CK, Weickhardt A, Townsend AR, Wrin JW, Chua A, Shivasami A, Cummins MM, Murone C, Tebbutt NC (2011) Impact of KRAS and BRAF gene mutation status on outcomes from the phase III AGITG MAX trial of capecitabine alone or in combination with bevacizumab and mitomycin in advanced colorectal cancer. J Clin Oncol 29:2675–2682. https://doi.org/10.1200/JCO.2010.34.5520 CrossRefPubMed

26.

Seligmann JF, Fisher D, Smith CG, Richman SD, Elliott F, Brown S, Adams R, Maughan T, Quirke P, Cheadle J, Seymour M, Middleton G (2016) Investigating the poor outcomes of BRAF -mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials. Ann Oncol mdw645. https://doi.org/10.1093/annonc/mdw645

27.

Benedix F, Kube R, Meyer F et al (2010) Colon/Rectum Carcinomas (Primary Tumor) Study Group. Comparison of 17,641 patients with right- and left-sided colon cancer: differences in epidemiology, perioperative course, histology, and survival. Dis Colon Rectum 53:57–64. https://doi.org/10.1007/DCR.0b013e3181c703a4. CrossRefPubMed

28.

Hanna MC, Go C, Roden C et al (2013) Colorectal cancers from distinct ancestral populations show variations in BRAF mutation frequency. PLoS One 8:e74950. https://doi.org/10.1371/journal.pone.0074950 CrossRefPubMedPubMedCentral

29.

Dejea CM, Wick EC, Hechenbleikner EM et al (2014) Microbiota organization is a distinct feature of proximal colorectal cancers. Proc Natl Acad Sci U S A 111:18321–18326. https://doi.org/10.1073/pnas.1406199111 CrossRefPubMedPubMedCentral

30.

Gao Z, Guo B, Gao R et al (2015) Microbiota disbiosis is associated with colorectal cancer. Front Microbiol 6:20. https://doi.org/10.3389/fmicb.2015.00020 PubMedPubMedCentralCrossRef

31.

Tahara T, Yamamoto E, Suzuki H et al (2014) Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res 74:1311–1318. https://doi.org/10.1158/0008-5472.CAN-13-1865 CrossRefPubMedPubMedCentral

32.

Taieb J, Le Malicot K, Shi Q et al (2017) Prognostic value of BRAF and KRAS mutations in MSI and MSS stage III colon cancer. J Natl Cancer Inst 109:djw272. https://doi.org/10.1093/jnci/djw272 CrossRef

33.

Taieb J, Zaanan A, Le Malicot K et al (2016) Prognostic effect of BRAF and KRAS mutations in patients with stage III colon cancer treated with leucovorin, fluorouracil, and oxaliplatin with or without cetuximab: a post hoc analysis of the PETACC-8 trial. JAMA Oncol 2:643. https://doi.org/10.1001/jamaoncol.2015.5225 CrossRef

34.

Dienstmann R, Mason MJ, Sinicrope FA et al (2017) Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study. Ann Oncol 28:1023–1031. https://doi.org/10.1093/annonc/mdx052 CrossRefPubMedPubMedCentral

35.

Tran B, Kopetz S, Tie J et al (2011) Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer 117:4623–4632. https://doi.org/10.1002/cncr.26086 CrossRefPubMedPubMedCentral

36.

Yaeger R, Cercek A, Chou JF et al (2014) BRAF mutation predicts for poor outcomes after metastasectomy in patients with metastatic colorectal cancer. Cancer 120:2316–2324. https://doi.org/10.1002/cncr.28729. CrossRefPubMedPubMedCentral

37.

Amri R, Bordeianou LG, Sylla P, Berger DL (2015) Variations in metastasis site by primary location in colon cancer. J Gastrointest Surg 19:1522–1527. https://doi.org/10.1007/s11605-015-2837-9 CrossRefPubMed

38.

Schrag D, Cramer LD, Bach PB, Begg CB (2001) Age and adjuvant chemotherapy use after surgery for stage III colon cancer. J Natl Cancer Inst 93:850–857CrossRefPubMed

39.

Hara M, Kanemitsu Y, Hirai T, Komori K, Kato T (2008) Negative serum carcinoembryonic antigen has insufficient accuracy for excluding recurrence from patients with Dukes C colorectal cancer: analysis with likelihood ratio and posttest probability in a follow-up study. Dis Colon Rectum 51:1675–1680. https://doi.org/10.1007/s10350-008-9406-1 CrossRefPubMed

40.

Cho M (2016) Impact of RAS and BRAF mutations on carcinoembryonic antigen production and pattern of colorectal metastases. World Journal of Gastrointestinal Oncology 8:128–135. https://doi.org/10.4251/wjgo.v8.i1.128 CrossRefPubMedPubMedCentral

41.

Kim JH, Kang GH (2014) Molecular and prognostic heterogeneity of microsatellite-unstable colorectal cancer. World J Gastroenterol 20:4230. https://doi.org/10.3748/wjg.v20.i15.4230 CrossRefPubMedPubMedCentral

42.

Barault L, Charon-Barra C, Jooste V, de la Vega MF, Martin L, Roignot P, Rat P, Bouvier AM, Laurent-Puig P, Faivre J, Chapusot C, Piard F (2008) Hypermethylator phenotype in sporadic colon cancer: study on a population-based series of 582 cases. Cancer Res 68:8541–8546. https://doi.org/10.1158/0008-5472.CAN-08-1171 CrossRefPubMed

43.

Richman SD, Seymour MT, Chambers P, Elliott F, Daly CL, Meade AM, Taylor G, Barrett JH, Quirke P (2009) KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial. J Clin Oncol 27:5931–5937. https://doi.org/10.1200/JCO.2009.22.4295 CrossRefPubMed

44.

Dahlin AM, Palmqvist R, Henriksson ML, Jacobsson M, Eklof V, Rutegard J, Oberg A, van Guelpen BR (2010) The role of the CpG island methylator phenotype in colorectal cancer prognosis depends on microsatellite instability screening status. Clin Cancer Res 16:1845–1855. https://doi.org/10.1158/1078-0432.CCR-09-2594 CrossRefPubMed

45.

Tie J, Gibbs P, Lipton L, Christie M, Jorissen RN, Burgess AW, Croxford M, Jones I, Langland R, Kosmider S, McKay D, Bollag G, Nolop K, Sieber OM, Desai J (2011) Optimizing targeted therapeutic development: analysis of a colorectal cancer patient population with the BRAFV600E mutation. Int J Cancer 128:2075–2084. https://doi.org/10.1002/ijc.25555 CrossRefPubMed

46.

Tian S, Simon I, Moreno V, Roepman P, Tabernero J, Snel M, van’t Veer L, Salazar R, Bernards R, Capella G (2013) A combined oncogenic pathway signature of BRAF , KRAS and PI3KCA mutation improves colorectal cancer classification and cetuximab treatment prediction. Gut 62:540–549. https://doi.org/10.1136/gutjnl-2012-302423 CrossRefPubMed

47.

Lochhead P, Kuchiba A, Imamura Y, Liao X, Yamauchi M, Nishihara R, Qian ZR, Morikawa T, Shen J, Meyerhardt JA, Fuchs CS, Ogino S (2013) Microsatellite instability and BRAF mutation testing in colorectal Cancer prognostication. JNCI: Journal of the National Cancer Institute 105:1151–1156. https://doi.org/10.1093/jnci/djt173 CrossRefPubMedPubMedCentral

48.

Li HT, Lu YY, An YX et al (2011) KRAS, BRAF and PIK3CA mutations in human colorectal cancer: relationship with metastatic colorectal cancer. Oncol Rep. https://doi.org/10.3892/or.2011.1217

49.

Nakanishi R, Harada J, Tuul M, Zhao Y, Ando K, Saeki H, Oki E, Ohga T, Kitao H, Kakeji Y, Maehara Y (2013) Prognostic relevance of KRAS and BRAF mutations in Japanese patients with colorectal cancer. Int J Clin Oncol 18:1042–1048. https://doi.org/10.1007/s10147-012-0501-x CrossRefPubMed

50.

Bae JM, Kim JH, Cho N-Y, Kim TY, Kang GH (2013) Prognostic implication of the CpG island methylator phenotype in colorectal cancers depends on tumour location. Br J Cancer 109:1004–1012. https://doi.org/10.1038/bjc.2013.430 CrossRefPubMedPubMedCentral

Titel: Clinical significance of the BRAFV600E mutation in Asian patients with colorectal cancer
verfasst von: Hou-Hsuan Cheng
Jen-Kou Lin
Wei-Shone Chen
Jeng-Kai Jiang
Shung-Haur Yang
Shih-Ching Chang
Publikationsdatum: 04.06.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: International Journal of Colorectal Disease / Ausgabe 9/2018
Print ISSN: 0179-1958
Elektronische ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-018-3095-6

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Clinical significance of the BRAFV600E mutation in Asian patients with colorectal cancer

Abstract

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Methods

Results

Conclusion

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