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Erschienen in: Virchows Archiv 6/2014

01.06.2014 | Original Article

VE1 immunohistochemistry accurately detects BRAF V600E mutations in colorectal carcinoma and can be utilized in the detection of poorly differentiated colorectal serrated adenocarcinoma

verfasst von: Sara Sajanti, Päivi Sirniö, Juha P. Väyrynen, Anne Tuomisto, Kai Klintrup, Jyrki Mäkelä, Ari Ristimäki, Markus J. Mäkinen

Erschienen in: Virchows Archiv | Ausgabe 6/2014

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Abstract

Serrated adenocarcinoma (SAC) is a recently defined subtype of colorectal carcinoma (CRC). However, in cases where an adjacent serrated adenoma is absent and the differentiation is poor, the diagnosis of SAC can be challenging. BRAF V600E mutation is a characteristic molecular change for the serrated route, but the utility of the newly described BRAF V600E-specific immunohistochemistry in the recognition of SAC is unclear. In this study, we conducted immunohistochemical determination of BRAF V600E mutation and correlated the results to BRAF mutation status and the histological features of SAC in a cohort of 147 CRC patients. There were 13 (8.8 %) BRAF-mutated CRCs confirmed by DNA sequencing. The sensitivity of immunohistochemistry in detecting BRAF V600E mutation was 100 % (13/13) and the specificity was 99.3 % (133/134). Three evaluators independently analyzed the immunohistochemical sections and the correlation between all the evaluators was perfect (κ = 1). In histologic examination, 33 (22.4 %) of the CRCs were classified as SACs. Twelve of 13 (92.3 %) BRAF-mutated CRCs were evaluated to represent serrated type growth pattern. One of 13 (7.7 %) showed poor differentiation not enabling convincing classification. In conclusion, we found immunohistochemistry to be accurate in the detection of the BRAF V600E mutation, with potential applications in the recognition of the BRAF-mutated SACs. Especially in cases where the adjacent adenoma is absent and the tumor is poorly differentiated, BRAF immunohistochemistry could be utilized as an aid to detect SACs.
Literatur
1.
Zurück zum Zitat Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249PubMedCrossRef Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249PubMedCrossRef
2.
Zurück zum Zitat Worthley DL, Leggett BA (2010) Colorectal cancer: molecular features and clinical opportunities. Clin Biochem Rev 31:31–38PubMedCentralPubMed Worthley DL, Leggett BA (2010) Colorectal cancer: molecular features and clinical opportunities. Clin Biochem Rev 31:31–38PubMedCentralPubMed
4.
Zurück zum Zitat Aaltonen LA, Salovaara R, Kristo P, Canzian F, Hemminki A, Peltomäki P, Chadwick RB, Kääriäinen H, Eskelinen M, Järvinen H, Mecklin JP, de la Chapelle A (1998) Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 338:1481–1487PubMedCrossRef Aaltonen LA, Salovaara R, Kristo P, Canzian F, Hemminki A, Peltomäki P, Chadwick RB, Kääriäinen H, Eskelinen M, Järvinen H, Mecklin JP, de la Chapelle A (1998) Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 338:1481–1487PubMedCrossRef
5.
Zurück zum Zitat Mäkinen MJ, George SM, Jernvall P, Mäkelä J, Vihko P, Karttunen TJ (2001) Colorectal carcinoma associated with serrated adenoma—prevalence, histological features, and prognosis. J Pathol 193:286–294PubMedCrossRef Mäkinen MJ, George SM, Jernvall P, Mäkelä J, Vihko P, Karttunen TJ (2001) Colorectal carcinoma associated with serrated adenoma—prevalence, histological features, and prognosis. J Pathol 193:286–294PubMedCrossRef
6.
Zurück zum Zitat Garcia-Solano J, Perez-Guillermo M, Conesa-Zamora P, Acosta-Ortega J, Trujillo-Santos J, Cerezuela-Fuentes P, Makinen MJ (2010) Clinicopathologic study of 85 colorectal serrated adenocarcinomas: further insights into the full recognition of a new subset of colorectal carcinoma. Hum Pathol 41(10):1359–1368PubMedCrossRef Garcia-Solano J, Perez-Guillermo M, Conesa-Zamora P, Acosta-Ortega J, Trujillo-Santos J, Cerezuela-Fuentes P, Makinen MJ (2010) Clinicopathologic study of 85 colorectal serrated adenocarcinomas: further insights into the full recognition of a new subset of colorectal carcinoma. Hum Pathol 41(10):1359–1368PubMedCrossRef
7.
Zurück zum Zitat Tuppurainen K, Mäkinen JM, Junttila O, Liakka A, Kyllönen AP, Tuominen H, Karttunen TJ, Mäkinen MJ (2005) Morphology and microsatellite instability in sporadic serrated and non-serrated colorectal cancer. J Pathol 207:285–294PubMedCrossRef Tuppurainen K, Mäkinen JM, Junttila O, Liakka A, Kyllönen AP, Tuominen H, Karttunen TJ, Mäkinen MJ (2005) Morphology and microsatellite instability in sporadic serrated and non-serrated colorectal cancer. J Pathol 207:285–294PubMedCrossRef
9.
Zurück zum Zitat Iino H, Jass JR, Simms LA, Young J, Leggett B, Ajioka Y, Watanabe H (1999) DNA microsatellite instability in hyperplastic polyps, serrated adenomas, and mixed polyps: a mild mutator pathway for colorectal cancer? J Clin Pathol 52:5–9PubMedCentralPubMedCrossRef Iino H, Jass JR, Simms LA, Young J, Leggett B, Ajioka Y, Watanabe H (1999) DNA microsatellite instability in hyperplastic polyps, serrated adenomas, and mixed polyps: a mild mutator pathway for colorectal cancer? J Clin Pathol 52:5–9PubMedCentralPubMedCrossRef
10.
Zurück zum Zitat Jass JR, Iino H, Ruszkiewicz A, Painter D, Solomon MJ, Koorey DJ, Cohn D, Furlong KL, Walsh MD, Palazzo J, Edmonston TB, Fishel R, Young J, Leggett BA (2000) Neoplastic progression occurs through mutator pathways in hyperplastic polyposis of the colorectum. Gut 47:43–49PubMedCentralPubMedCrossRef Jass JR, Iino H, Ruszkiewicz A, Painter D, Solomon MJ, Koorey DJ, Cohn D, Furlong KL, Walsh MD, Palazzo J, Edmonston TB, Fishel R, Young J, Leggett BA (2000) Neoplastic progression occurs through mutator pathways in hyperplastic polyposis of the colorectum. Gut 47:43–49PubMedCentralPubMedCrossRef
11.
Zurück zum Zitat McGivern A, Wynter CV, Whitehall VL, Kambara T, Spring KJ, Walsh MD, Barker MA, Arnold S, Simms LA, Leggett BA, Young J, Jass JR (2004) Promoter hypermethylation frequency and BRAF mutations distinguish hereditary non-polyposis colon cancer from sporadic MSI-H colon cancer. Fam Cancer 3:101–107PubMedCrossRef McGivern A, Wynter CV, Whitehall VL, Kambara T, Spring KJ, Walsh MD, Barker MA, Arnold S, Simms LA, Leggett BA, Young J, Jass JR (2004) Promoter hypermethylation frequency and BRAF mutations distinguish hereditary non-polyposis colon cancer from sporadic MSI-H colon cancer. Fam Cancer 3:101–107PubMedCrossRef
12.
Zurück zum Zitat Poynter JN, Siegmund KD, Weisenberger DJ, Long TI, Thibodeau SN, Lindor N, Young J, Jenkins MA, Hopper JL, Baron JA, Buchanan D, Casey G, Levine AJ, Le Marchand L, Gallinger S, Bapat B, Potter JD, Newcomb PA, Haile RW, Laird PW, Colon Cancer Family Registry Investigators (2008) Molecular characterization of MSI-H colorectal cancer by MLHI promoter methylation, immunohistochemistry, and mismatch repair germline mutation screening. Cancer Epidemiol Biomarkers Prev 17:3208–3215CrossRef Poynter JN, Siegmund KD, Weisenberger DJ, Long TI, Thibodeau SN, Lindor N, Young J, Jenkins MA, Hopper JL, Baron JA, Buchanan D, Casey G, Levine AJ, Le Marchand L, Gallinger S, Bapat B, Potter JD, Newcomb PA, Haile RW, Laird PW, Colon Cancer Family Registry Investigators (2008) Molecular characterization of MSI-H colorectal cancer by MLHI promoter methylation, immunohistochemistry, and mismatch repair germline mutation screening. Cancer Epidemiol Biomarkers Prev 17:3208–3215CrossRef
13.
Zurück zum Zitat Kambara T, Simms LA, Whitehall VL, Spring KJ, Wynter CV, Walsh MD, Barker MA, Arnold S, McGivern A, Matsubara N, Tanaka N, Higuchi T, Young J, Jass JR, Leggett BA (2004) BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut 53:1137–1144PubMedCentralPubMedCrossRef Kambara T, Simms LA, Whitehall VL, Spring KJ, Wynter CV, Walsh MD, Barker MA, Arnold S, McGivern A, Matsubara N, Tanaka N, Higuchi T, Young J, Jass JR, Leggett BA (2004) BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut 53:1137–1144PubMedCentralPubMedCrossRef
14.
Zurück zum Zitat O’Brien MJ, Yang S, Mack C, Xu H, Huang CS, Mulcahy E, Amorosino M, Farraye FA (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 30:1491–1501PubMedCrossRef O’Brien MJ, Yang S, Mack C, Xu H, Huang CS, Mulcahy E, Amorosino M, Farraye FA (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 30:1491–1501PubMedCrossRef
15.
Zurück zum Zitat Patil DT, Shadrach BL, Rybicki LA, Leach BH, Pai RK (2012) Proximal colon cancers and the serrated pathway: a systematic analysis of precursor histology and BRAF mutation status. Mod Pathol 25:1423–1431PubMedCrossRef Patil DT, Shadrach BL, Rybicki LA, Leach BH, Pai RK (2012) Proximal colon cancers and the serrated pathway: a systematic analysis of precursor histology and BRAF mutation status. Mod Pathol 25:1423–1431PubMedCrossRef
16.
Zurück zum Zitat Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA (2002) Mutations of the BRAF gene in human cancer. Nature 417:949–954PubMedCrossRef Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA (2002) Mutations of the BRAF gene in human cancer. Nature 417:949–954PubMedCrossRef
17.
Zurück zum Zitat Schlessinger J (2002) Ligand-induced, receptor-mediated dimerization and activation of EGF receptor. Cell 110:669–672PubMedCrossRef Schlessinger J (2002) Ligand-induced, receptor-mediated dimerization and activation of EGF receptor. Cell 110:669–672PubMedCrossRef
18.
Zurück zum Zitat Nagasaka T, Sasamoto H, Notohara K, Cullings HM, Takeda M, Kimura K, Kambara T, MacPhee DG, Young J, Leggett BA, Jass JR, Tanaka N, Matsubara N (2004) Colorectal cancer with mutation in BRAF, KRAS, and wild-type with respect to both oncogenes showing different patterns of DNA methylation. J Clin Oncol 22:4584–4594PubMedCrossRef Nagasaka T, Sasamoto H, Notohara K, Cullings HM, Takeda M, Kimura K, Kambara T, MacPhee DG, Young J, Leggett BA, Jass JR, Tanaka N, Matsubara N (2004) Colorectal cancer with mutation in BRAF, KRAS, and wild-type with respect to both oncogenes showing different patterns of DNA methylation. J Clin Oncol 22:4584–4594PubMedCrossRef
19.
Zurück zum Zitat Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, Kang GH, Widschwendter M, Weener D, Buchanan D, Koh H, Simms L, Barker M, Leggett B, Levine J, Kim M, French AJ, Thibodeau SN, Jass J, Haile R, Laird PW (2006) CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 38:787–793PubMedCrossRef Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, Kang GH, Widschwendter M, Weener D, Buchanan D, Koh H, Simms L, Barker M, Leggett B, Levine J, Kim M, French AJ, Thibodeau SN, Jass J, Haile R, Laird PW (2006) CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 38:787–793PubMedCrossRef
20.
Zurück zum Zitat Long GV, Wilmott JS, Capper D, Preusser M, Zhang YE, Thompson JF, Kefford RF, von Deimling A, Scolyer RA (2013) Immunohistochemistry is highly sensitive and specific for the detection of V600E BRAF mutation in melanoma. Am J Surg Pathol 37:61–65PubMedCrossRef Long GV, Wilmott JS, Capper D, Preusser M, Zhang YE, Thompson JF, Kefford RF, von Deimling A, Scolyer RA (2013) Immunohistochemistry is highly sensitive and specific for the detection of V600E BRAF mutation in melanoma. Am J Surg Pathol 37:61–65PubMedCrossRef
21.
Zurück zum Zitat Sinicrope FA, Smyrk TC, Tougeron D, Thibodeau SN, Singh S, Muranyi A, Shanmugam K, Grogan TM, Alberts SR, Shi Q (2013) Mutation-specific antibody detects mutant BRAF(V600E) protein expression in human colon carcinomas. Cancer 119:2765–2770PubMedCrossRef Sinicrope FA, Smyrk TC, Tougeron D, Thibodeau SN, Singh S, Muranyi A, Shanmugam K, Grogan TM, Alberts SR, Shi Q (2013) Mutation-specific antibody detects mutant BRAF(V600E) protein expression in human colon carcinomas. Cancer 119:2765–2770PubMedCrossRef
22.
Zurück zum Zitat Affolter K, Samowitz W, Tripp S, Bronner MP (2013) BRAF V600E mutation detection by immunohistochemistry in colorectal carcinoma. Genes Chromosomes Cancer 52:748–752PubMedCrossRef Affolter K, Samowitz W, Tripp S, Bronner MP (2013) BRAF V600E mutation detection by immunohistochemistry in colorectal carcinoma. Genes Chromosomes Cancer 52:748–752PubMedCrossRef
23.
Zurück zum Zitat Thiel A, Heinonen M, Kantonen J, Gylling A, Lahtinen L, Korhonen M, Kytölä S, Mecklin JP, Orpana A, Peltomäki P, Ristimäki A (2013) BRAF mutation in sporadic colorectal cancer and Lynch syndrome. Virchows Arch 463(5):613–621PubMedCrossRef Thiel A, Heinonen M, Kantonen J, Gylling A, Lahtinen L, Korhonen M, Kytölä S, Mecklin JP, Orpana A, Peltomäki P, Ristimäki A (2013) BRAF mutation in sporadic colorectal cancer and Lynch syndrome. Virchows Arch 463(5):613–621PubMedCrossRef
24.
Zurück zum Zitat Stefanius K, Ylitalo L, Tuomisto A, Kuivila R, Kantola T, Sirnio P, Karttunen TJ, Mäkinen MJ (2011) Frequent mutations of KRAS in addition to BRAF in colorectal serrated adenocarcinoma. Histopathology 58:679–692PubMedCentralPubMedCrossRef Stefanius K, Ylitalo L, Tuomisto A, Kuivila R, Kantola T, Sirnio P, Karttunen TJ, Mäkinen MJ (2011) Frequent mutations of KRAS in addition to BRAF in colorectal serrated adenocarcinoma. Histopathology 58:679–692PubMedCentralPubMedCrossRef
25.
Zurück zum Zitat Kantola T, Klintrup K, Väyrynen JP, Vornanen J, Bloigu R, Karhu T, Herzig K, Näpänkangas J, Mäkelä J, Karttunen TJ, Tuomisto A, Mäkinen MJ (2012) Stage-dependent alterations of the serum cytokine pattern in colorectal carcinoma. Br J Cancer 107:1729–1736PubMedCentralPubMedCrossRef Kantola T, Klintrup K, Väyrynen JP, Vornanen J, Bloigu R, Karhu T, Herzig K, Näpänkangas J, Mäkelä J, Karttunen TJ, Tuomisto A, Mäkinen MJ (2012) Stage-dependent alterations of the serum cytokine pattern in colorectal carcinoma. Br J Cancer 107:1729–1736PubMedCentralPubMedCrossRef
26.
Zurück zum Zitat Hamilton SR, Bosman FT, Boffetta P, Ilyas M, Morreau H, Nakamura S, Quirke P, Riboli E, Sobin LH (2010) Carcinoma of the colon and rectum. In: Bosman FT, Carneiro F, Hruban RH, Theise ND (eds) WHO classification of tumours of the digestive system, 4th edn. IARC, Lyon, pp 134–146 Hamilton SR, Bosman FT, Boffetta P, Ilyas M, Morreau H, Nakamura S, Quirke P, Riboli E, Sobin LH (2010) Carcinoma of the colon and rectum. In: Bosman FT, Carneiro F, Hruban RH, Theise ND (eds) WHO classification of tumours of the digestive system, 4th edn. IARC, Lyon, pp 134–146
27.
Zurück zum Zitat Garcia-Solano J, Conesa-Zamora P, Carbonell P, Trujillo-Santos J, Torres-Moreno DD, Pagan-Gomez I, Rodriguez-Braun E, Perez-Guillermo M (2012) Colorectal serrated adenocarcinoma shows a different profile of oncogene mutations, MSI status and DNA repair protein expression compared to conventional and sporadic MSI-H carcinomas. Int J Cancer 131:1790–1799PubMedCrossRef Garcia-Solano J, Conesa-Zamora P, Carbonell P, Trujillo-Santos J, Torres-Moreno DD, Pagan-Gomez I, Rodriguez-Braun E, Perez-Guillermo M (2012) Colorectal serrated adenocarcinoma shows a different profile of oncogene mutations, MSI status and DNA repair protein expression compared to conventional and sporadic MSI-H carcinomas. Int J Cancer 131:1790–1799PubMedCrossRef
28.
Zurück zum Zitat Capper D, Voigt A, Bozukova G, Ahadova A, Kickingereder P, von Deimling A, von Knebel DM, Kloor M (2013) BRAF V600E-specific immunohistochemistry for the exclusion of Lynch syndrome in MSI-H colorectal cancer. Int J Cancer 133:1624–1630PubMedCrossRef Capper D, Voigt A, Bozukova G, Ahadova A, Kickingereder P, von Deimling A, von Knebel DM, Kloor M (2013) BRAF V600E-specific immunohistochemistry for the exclusion of Lynch syndrome in MSI-H colorectal cancer. Int J Cancer 133:1624–1630PubMedCrossRef
29.
Zurück zum Zitat Toon CW, Walsh MD, Chou A, Capper D, Clarkson A, Sioson L, Clarke S, Mead S, Walters RJ, Clendenning M, Rosty C, Young JP, Win AK, Hopper JL, Crook A, von Deimling A, Jenkins MA, Buchanan DD, Gill AJ (2013) BRAFV600e immunohistochemistry facilitates universal screening of colorectal cancers for Lynch syndrome. Am J Surg Pathol 37:1592–1602PubMedCrossRef Toon CW, Walsh MD, Chou A, Capper D, Clarkson A, Sioson L, Clarke S, Mead S, Walters RJ, Clendenning M, Rosty C, Young JP, Win AK, Hopper JL, Crook A, von Deimling A, Jenkins MA, Buchanan DD, Gill AJ (2013) BRAFV600e immunohistochemistry facilitates universal screening of colorectal cancers for Lynch syndrome. Am J Surg Pathol 37:1592–1602PubMedCrossRef
30.
Zurück zum Zitat Jin M, Hampel H, Zhou X, Schunemann L, Yearsley M, Frankel WL (2013) BRAF V600E mutation analysis simplifies the testing algorithm for Lynch syndrome. Am J Clin Pathol 140:177–183PubMedCrossRef Jin M, Hampel H, Zhou X, Schunemann L, Yearsley M, Frankel WL (2013) BRAF V600E mutation analysis simplifies the testing algorithm for Lynch syndrome. Am J Clin Pathol 140:177–183PubMedCrossRef
31.
Zurück zum Zitat Parsons MT, Buchanan DD, Thompson B, Young JP, Spurdle AB (2012) Correlation of tumour BRAF mutations and MLH1 methylation with germline mismatch repair (MMR) gene mutation status: a literature review assessing utility of tumour features for MMR variant classification. J Med Genet 49:151–157PubMedCrossRef Parsons MT, Buchanan DD, Thompson B, Young JP, Spurdle AB (2012) Correlation of tumour BRAF mutations and MLH1 methylation with germline mismatch repair (MMR) gene mutation status: a literature review assessing utility of tumour features for MMR variant classification. J Med Genet 49:151–157PubMedCrossRef
32.
Zurück zum Zitat Mesteri I, Bayer G, Meyer J, Capper D, Schoppmann SF, von Deimling A, Birner P (2014) Improved molecular classification of serrated lesions of the colon by immunohistochemical detection of BRAF V600E. Mod Pathol 27(1):135–144PubMedCrossRef Mesteri I, Bayer G, Meyer J, Capper D, Schoppmann SF, von Deimling A, Birner P (2014) Improved molecular classification of serrated lesions of the colon by immunohistochemical detection of BRAF V600E. Mod Pathol 27(1):135–144PubMedCrossRef
33.
Zurück zum Zitat Spring KJ, Zhao ZZ, Karamatic R, Walsh MD, Whitehall VL, Pike T, Simms LA, Young J, James M, Montgomery GW, Appleyard M, Hewett D, Togashi K, Jass JR, Leggett BA (2006) High prevalence of sessile serrated adenomas with BRAF mutations: a prospective study of patients undergoing colonoscopy. Gastroenterology 131:1400–1407PubMedCrossRef Spring KJ, Zhao ZZ, Karamatic R, Walsh MD, Whitehall VL, Pike T, Simms LA, Young J, James M, Montgomery GW, Appleyard M, Hewett D, Togashi K, Jass JR, Leggett BA (2006) High prevalence of sessile serrated adenomas with BRAF mutations: a prospective study of patients undergoing colonoscopy. Gastroenterology 131:1400–1407PubMedCrossRef
34.
Zurück zum Zitat Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, Zanon C, Moroni M, Veronese S, Siena S, Bardelli A (2007) 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 67:2643–2648PubMedCrossRef Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, Zanon C, Moroni M, Veronese S, Siena S, Bardelli A (2007) 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 67:2643–2648PubMedCrossRef
35.
Zurück zum Zitat Lievre A, Blons H, Laurent-Puig P (2010) Oncogenic mutations as predictive factors in colorectal cancer. Oncogene 29:3033–3043PubMedCrossRef Lievre A, Blons H, Laurent-Puig P (2010) Oncogenic mutations as predictive factors in colorectal cancer. Oncogene 29:3033–3043PubMedCrossRef
36.
Zurück zum Zitat Mao C, Liao RY, Qiu LX, Wang XW, Ding H, Chen Q (2011) BRAF V600E mutation and resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer: a meta-analysis. Mol Biol Rep 38:2219–2223PubMedCrossRef Mao C, Liao RY, Qiu LX, Wang XW, Ding H, Chen Q (2011) BRAF V600E mutation and resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer: a meta-analysis. Mol Biol Rep 38:2219–2223PubMedCrossRef
37.
Zurück zum Zitat Peyssonnaux C, Eychene A (2001) The Raf/MEK/ERK pathway: new concepts of activation. Biol Cell 93:53–62PubMedCrossRef Peyssonnaux C, Eychene A (2001) The Raf/MEK/ERK pathway: new concepts of activation. Biol Cell 93:53–62PubMedCrossRef
38.
Zurück zum Zitat Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O’Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA, BRIM-3 Study Group (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364:2507–2516PubMedCentralPubMedCrossRef Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O’Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA, BRIM-3 Study Group (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364:2507–2516PubMedCentralPubMedCrossRef
39.
Zurück zum Zitat Coffee EM, Faber AC, Roper J, Sinnamon MJ, Goel G, Keung L, Wang WV, Vecchione L, de Vriendt V, Weinstein BJ, Bronson RT, Tejpar S, Xavier RJ, Engelman JA, Martin ES, Hung KE (2013) Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer. Clin Cancer Res 19:2688–2698PubMedCrossRef Coffee EM, Faber AC, Roper J, Sinnamon MJ, Goel G, Keung L, Wang WV, Vecchione L, de Vriendt V, Weinstein BJ, Bronson RT, Tejpar S, Xavier RJ, Engelman JA, Martin ES, Hung KE (2013) Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer. Clin Cancer Res 19:2688–2698PubMedCrossRef
Metadaten
Titel
VE1 immunohistochemistry accurately detects BRAF V600E mutations in colorectal carcinoma and can be utilized in the detection of poorly differentiated colorectal serrated adenocarcinoma
verfasst von
Sara Sajanti
Päivi Sirniö
Juha P. Väyrynen
Anne Tuomisto
Kai Klintrup
Jyrki Mäkelä
Ari Ristimäki
Markus J. Mäkinen
Publikationsdatum
01.06.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Virchows Archiv / Ausgabe 6/2014
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-014-1555-0

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