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Erschienen in: Journal of Cancer Research and Clinical Oncology 1/2017

26.09.2016 | Original Article – Clinical Oncology

Prognostic value of BRAF V600E mutation and microsatellite instability in Japanese patients with sporadic colorectal cancer

verfasst von: Yu Nakaji, Eiji Oki, Ryota Nakanishi, Koji Ando, Masahiko Sugiyama, Yuichiro Nakashima, Nami Yamashita, Hiroshi Saeki, Yoshinao Oda, Yoshihiko Maehara

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 1/2017

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Abstract

Purpose

In colorectal cancer (CRC), the BRAF V600E mutation is an important biomarker for poor prognosis, while high microsatellite instability (MSI-H) indicates good prognosis. Using a commercial BRAF V600E-specific antibody, we investigated the BRAF V600E mutation according to immunohistochemistry (IHC) and the MSI status in Japanese patients with CRC.

Methods

In this retrospective study, tissue samples from 472 Japanese patients with CRC, stratified for MSI, were analyzed to determine the prognostic value of BRAF V600E, as assessed using IHC. Mutations in 254 patients were evaluated using the direct sequencing method to check for concordance.

Results

The frequency of MSI-H was 9.3 % (44/472), and BRAF V600E mutation was detected immunohistochemically in 8.7 % patients (41/472). The sensitivity and specificity for detection of BRAF V600E mutations by IHC were 100 % (17/17) and 98.7 % (234/237), respectively. BRAF V600E mutations were significantly correlated with the anatomical tumor site (P = 0.0035), histological type (P < 0.0001), and MSI status (P < 0.0001). Consistent with other published series, patients with BRAF V600E mutation exhibited a significantly shorter overall survival (hazard ratio = 1.500, P = 0.0432). In particular, the microsatellite stable/BRAF mutation group had inferior prognosis compared with the MSI-H/BRAF wild-type group (hazard ratio = 2.621, P = 0.0004).

Conclusions

IHC using a BRAF V600E-specific antibody was useful for diagnosis and concurred with direct sequencing results. CRC cases could be stratified by combining BRAF V600E mutation and MSI status as a prognostic factor in Japanese patients.
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Literatur
Zurück zum Zitat 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 68:8541–8546CrossRefPubMed 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 68:8541–8546CrossRefPubMed
Zurück zum Zitat Blaker H, Helmchen B, Bonisch A, Aulmann S, Penzel R, Otto HF, Rieker RJ (2004) Mutational activation of the RAS-RAF-MAPK and the Wnt pathway in small intestinal adenocarcinomas. Scand J Gastroenterol 39:748–753CrossRefPubMed Blaker H, Helmchen B, Bonisch A, Aulmann S, Penzel R, Otto HF, Rieker RJ (2004) Mutational activation of the RAS-RAF-MAPK and the Wnt pathway in small intestinal adenocarcinomas. Scand J Gastroenterol 39:748–753CrossRefPubMed
Zurück zum Zitat Bosman FT, Yan P (2014) Molecular pathology of colorectal cancer. Pol J Pathol 4:257–266CrossRef Bosman FT, Yan P (2014) Molecular pathology of colorectal cancer. Pol J Pathol 4:257–266CrossRef
Zurück zum Zitat Colombino M, Sperlongano P, Izzo F, Tatangelo F, Botti G, Lombardi A, Accardo M, Tarantino L, Sordelli I, Agresti M, Abbruzzese A, Caraglia M, Palmieri G (2012) BRAF and PIK3CA genes are somatically mutated in hepatocellular carcinoma among patients from South Italy. Cell Death Dis 3:e259CrossRefPubMedPubMedCentral Colombino M, Sperlongano P, Izzo F, Tatangelo F, Botti G, Lombardi A, Accardo M, Tarantino L, Sordelli I, Agresti M, Abbruzzese A, Caraglia M, Palmieri G (2012) BRAF and PIK3CA genes are somatically mutated in hepatocellular carcinoma among patients from South Italy. Cell Death Dis 3:e259CrossRefPubMedPubMedCentral
Zurück zum Zitat Curtin K, Slattery ML, Samowitz WS (2011) CpG island methylation in colorectal cancer: past, present and future. Pathol Res Int 2011:902674CrossRef Curtin K, Slattery ML, Samowitz WS (2011) CpG island methylation in colorectal cancer: past, present and future. Pathol Res Int 2011:902674CrossRef
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 JWC, 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 417:949–954CrossRefPubMed 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 JWC, 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 417:949–954CrossRefPubMed
Zurück zum Zitat Day F, Muranyi A, Singh S, Shanmugam K, Williams D, Byrne D, Pham K, Palmieri M, Tie J, Grogan T, Gibbs P, Sieber O, Waring P, Desai J (2015) A mutant BRAF V600E-specific immunohistochemical assay: correlation with molecular mutation status and clinical outcome in colorectal cancer. Target Oncol 10:99–109CrossRefPubMed Day F, Muranyi A, Singh S, Shanmugam K, Williams D, Byrne D, Pham K, Palmieri M, Tie J, Grogan T, Gibbs P, Sieber O, Waring P, Desai J (2015) A mutant BRAF V600E-specific immunohistochemical assay: correlation with molecular mutation status and clinical outcome in colorectal cancer. Target Oncol 10:99–109CrossRefPubMed
Zurück zum Zitat French AJ, Sargent DJ, Burgart LJ, Foster NR, Kabat BF, Goldberg R, Shepherd L, Windschitl HE, Thibodeau SN (2008) Prognostic significance of defective mismatch repair and BRAF V600E in patients with colon cancer. Clin Cancer Res Off J Am Assoc Cancer Res 14:3408–3415CrossRef French AJ, Sargent DJ, Burgart LJ, Foster NR, Kabat BF, Goldberg R, Shepherd L, Windschitl HE, Thibodeau SN (2008) Prognostic significance of defective mismatch repair and BRAF V600E in patients with colon cancer. Clin Cancer Res Off J Am Assoc Cancer Res 14:3408–3415CrossRef
Zurück zum Zitat Garnett MJ, Marais R (2004) Guilty as charged: B-RAF is a human oncogene. Cancer Cell 6:313–319CrossRefPubMed Garnett MJ, Marais R (2004) Guilty as charged: B-RAF is a human oncogene. Cancer Cell 6:313–319CrossRefPubMed
Zurück zum Zitat Goeppert B, Frauenschuh L, Renner M, Roessler S, Stenzinger A, Klauschen F, Warth A, Vogel MN, Mehrabi A, Hafezi M, Boehmer K, von Deimling A, Schirmacher P, Weichert W, Capper D (2014) BRAF V600E-specific immunohistochemistry reveals low mutation rates in biliary tract cancer and restriction to intrahepatic cholangiocarcinoma. Modern Pathol Off J US Can Acad Pathol Inc 27:1028–1034 Goeppert B, Frauenschuh L, Renner M, Roessler S, Stenzinger A, Klauschen F, Warth A, Vogel MN, Mehrabi A, Hafezi M, Boehmer K, von Deimling A, Schirmacher P, Weichert W, Capper D (2014) BRAF V600E-specific immunohistochemistry reveals low mutation rates in biliary tract cancer and restriction to intrahepatic cholangiocarcinoma. Modern Pathol Off J US Can Acad Pathol Inc 27:1028–1034
Zurück zum Zitat Ishimura N, Yamasawa K, Rumi MAK, Kadowaki Y, Ishihara S, Amano Y, Nio Y, Higami T, Kinoshita Y (2003) BRAF and K-ras gene mutations in human pancreatic cancers. Cancer Lett 199:169–173CrossRefPubMed Ishimura N, Yamasawa K, Rumi MAK, Kadowaki Y, Ishihara S, Amano Y, Nio Y, Higami T, Kinoshita Y (2003) BRAF and K-ras gene mutations in human pancreatic cancers. Cancer Lett 199:169–173CrossRefPubMed
Zurück zum Zitat Jass JR (2007) Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology 50:113–130CrossRefPubMed Jass JR (2007) Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology 50:113–130CrossRefPubMed
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 53:1137–1144CrossRefPubMedPubMedCentral 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 53:1137–1144CrossRefPubMedPubMedCentral
Zurück zum Zitat Kuan SF, Navina S, Cressman KL, Pai RK (2014) Immunohistochemical detection of BRAF V600E mutant protein using the VE1 antibody in colorectal carcinoma is highly concordant with molecular testing but requires rigorous antibody optimization. Hum Pathol 45:464–472CrossRefPubMed Kuan SF, Navina S, Cressman KL, Pai RK (2014) Immunohistochemical detection of BRAF V600E mutant protein using the VE1 antibody in colorectal carcinoma is highly concordant with molecular testing but requires rigorous antibody optimization. Hum Pathol 45:464–472CrossRefPubMed
Zurück zum Zitat 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. J Natl Cancer Inst 105:1151–1156CrossRefPubMedPubMedCentral 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. J Natl Cancer Inst 105:1151–1156CrossRefPubMedPubMedCentral
Zurück zum Zitat Loupakis F, Cremolini C, Salvatore L, Masi G, Sensi E, Schirripa M, Michelucci A, Pfanner E, Brunetti I, Lupi C, Antoniotti C, Bergamo F, Lonardi S, Zagonel V, Simi P, Fontanini G, Falcone A (2014) FOLFOXIRI plus bevacizumab as first-line treatment in BRAF mutant metastatic colorectal cancer. Eur J Cancer 50:57–63CrossRefPubMed Loupakis F, Cremolini C, Salvatore L, Masi G, Sensi E, Schirripa M, Michelucci A, Pfanner E, Brunetti I, Lupi C, Antoniotti C, Bergamo F, Lonardi S, Zagonel V, Simi P, Fontanini G, Falcone A (2014) FOLFOXIRI plus bevacizumab as first-line treatment in BRAF mutant metastatic colorectal cancer. Eur J Cancer 50:57–63CrossRefPubMed
Zurück zum Zitat Maeng CH, Lee J, van Hummelen P, Park SH, Palescandolo E, Jang J, Park HY, Kang SY, MacConaill L, Kim KM, Shim YM (2012) High-throughput genotyping in metastatic esophageal squamous cell carcinoma identifies phosphoinositide-3-kinase and BRAF mutations. PLoS ONE 7:e41655CrossRefPubMedPubMedCentral Maeng CH, Lee J, van Hummelen P, Park SH, Palescandolo E, Jang J, Park HY, Kang SY, MacConaill L, Kim KM, Shim YM (2012) High-throughput genotyping in metastatic esophageal squamous cell carcinoma identifies phosphoinositide-3-kinase and BRAF mutations. PLoS ONE 7:e41655CrossRefPubMedPubMedCentral
Zurück zum Zitat Moreira L, Balaguer F, Lindor N, de la Chapelle A, Hampel H, Aaltonen LA, Hopper JL, Le Marchand L, Gallinger S, Newcomb PA, Haile R, Thibodeau SN, Gunawardena S, Jenkins MA, Buchanan DD, Potter JD, Baron JA, Ahnen DJ, Moreno V, Andreu M, Ponz de Leon M, Rustgi AK, Castells A, Consortium E (2012) Identification of Lynch syndrome among patients with colorectal cancer. JAMA 308:1555–1565CrossRefPubMed Moreira L, Balaguer F, Lindor N, de la Chapelle A, Hampel H, Aaltonen LA, Hopper JL, Le Marchand L, Gallinger S, Newcomb PA, Haile R, Thibodeau SN, Gunawardena S, Jenkins MA, Buchanan DD, Potter JD, Baron JA, Ahnen DJ, Moreno V, Andreu M, Ponz de Leon M, Rustgi AK, Castells A, Consortium E (2012) Identification of Lynch syndrome among patients with colorectal cancer. JAMA 308:1555–1565CrossRefPubMed
Zurück zum Zitat 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 18:1042–1048CrossRefPubMed 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 18:1042–1048CrossRefPubMed
Zurück zum Zitat Oda S, Oki E, Maehara Y, Sugimachi K (1997) Precise assessment of microsatellite instability using high resolution fluorescent microsatellite analysis. Nucleic Acids Res 25:3415–3420CrossRefPubMedPubMedCentral Oda S, Oki E, Maehara Y, Sugimachi K (1997) Precise assessment of microsatellite instability using high resolution fluorescent microsatellite analysis. Nucleic Acids Res 25:3415–3420CrossRefPubMedPubMedCentral
Zurück zum Zitat Ogura T, Kakuta M, Yatsuoka T, Nishimura Y, Sakamoto H, Yamaguchi K, Tanabe M, Tanaka Y, Akagi K (2014) Clinicopathological characteristics and prognostic impact of colorectal cancers with NRAS mutations. Oncol Rep 32:50–56PubMed Ogura T, Kakuta M, Yatsuoka T, Nishimura Y, Sakamoto H, Yamaguchi K, Tanabe M, Tanaka Y, Akagi K (2014) Clinicopathological characteristics and prognostic impact of colorectal cancers with NRAS mutations. Oncol Rep 32:50–56PubMed
Zurück zum Zitat Oki E, Oda S, Maehara Y, Sugimachi K (1999) Mutated gene-specific phenotypes of dinucleotide repeat instability in human colorectal carcinoma cell lines deficient in DNA mismatch repair. Oncogene 18:2143–2147CrossRefPubMed Oki E, Oda S, Maehara Y, Sugimachi K (1999) Mutated gene-specific phenotypes of dinucleotide repeat instability in human colorectal carcinoma cell lines deficient in DNA mismatch repair. Oncogene 18:2143–2147CrossRefPubMed
Zurück zum Zitat Phipps AI, Limburg PJ, Baron JA, Burnett-Hartman AN, Weisenberger DJ, Laird PW, Sinicrope FA, Rosty C, Buchanan DD, Potter JD, Newcomb PA (2015) Association between molecular subtypes of colorectal cancer and patient survival. Gastroenterology 148(77–87):e72 Phipps AI, Limburg PJ, Baron JA, Burnett-Hartman AN, Weisenberger DJ, Laird PW, Sinicrope FA, Rosty C, Buchanan DD, Potter JD, Newcomb PA (2015) Association between molecular subtypes of colorectal cancer and patient survival. Gastroenterology 148(77–87):e72
Zurück zum Zitat Qiu T, Lu H, Guo L, Huang W, Ling Y, Shan L, Li W, Ying J, Lv N (2015) Detection of BRAF mutation in Chinese tumor patients using a highly sensitive antibody immunohistochemistry assay. Sci Rep 5:9211CrossRefPubMedPubMedCentral Qiu T, Lu H, Guo L, Huang W, Ling Y, Shan L, Li W, Ying J, Lv N (2015) Detection of BRAF mutation in Chinese tumor patients using a highly sensitive antibody immunohistochemistry assay. Sci Rep 5:9211CrossRefPubMedPubMedCentral
Zurück zum Zitat Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE (2002) Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature 418:934CrossRefPubMed Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE (2002) Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature 418:934CrossRefPubMed
Zurück zum Zitat Roth AD, Tejpar S, Delorenzi M, Yan P, Fiocca R, Klingbiel D, Dietrich D, Biesmans B, Bodoky G, Barone C, Aranda E, Nordlinger B, Cisar L, Labianca R, Cunningham D, Van Cutsem E, Bosman F (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 28:466–474CrossRef Roth AD, Tejpar S, Delorenzi M, Yan P, Fiocca R, Klingbiel D, Dietrich D, Biesmans B, Bodoky G, Barone C, Aranda E, Nordlinger B, Cisar L, Labianca R, Cunningham D, Van Cutsem E, Bosman F (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 28:466–474CrossRef
Zurück zum Zitat Stachler MD, Rinehart E, Lindeman N, Odze R, Srivastava A (2015) Novel molecular insights from routine genotyping of colorectal carcinomas. Hum Pathol 46:507–513CrossRefPubMed Stachler MD, Rinehart E, Lindeman N, Odze R, Srivastava A (2015) Novel molecular insights from routine genotyping of colorectal carcinomas. Hum Pathol 46:507–513CrossRefPubMed
Zurück zum Zitat Thiel A, Heinonen M, Kantonen J, Gylling A, Lahtinen L, Korhonen M, Kytola S, Mecklin JP, Orpana A, Peltomaki P, Ristimaki A (2013) BRAF mutation in sporadic colorectal cancer and Lynch syndrome. Virchows Arch Int J Pathol 463:613–621CrossRef Thiel A, Heinonen M, Kantonen J, Gylling A, Lahtinen L, Korhonen M, Kytola S, Mecklin JP, Orpana A, Peltomaki P, Ristimaki A (2013) BRAF mutation in sporadic colorectal cancer and Lynch syndrome. Virchows Arch Int J Pathol 463:613–621CrossRef
Zurück zum Zitat Toh Y, Oki E, Oda S, Tomoda M, Tomisaki S, Ichiyoshi Y, Ohno S, Sugimachi K (1996) An integrated microsatellite length analysis using an automated fluorescent DNA sequencer. Cancer Res 56:2688–2691PubMed Toh Y, Oki E, Oda S, Tomoda M, Tomisaki S, Ichiyoshi Y, Ohno S, Sugimachi K (1996) An integrated microsatellite length analysis using an automated fluorescent DNA sequencer. Cancer Res 56:2688–2691PubMed
Zurück zum Zitat Toon CW, Chou A, DeSilva K, Chan J, Patterson J, Clarkson A, Sioson L, Jankova L, Gill AJ (2014) BRAFV600E immunohistochemistry in conjunction with mismatch repair status predicts survival in patients with colorectal cancer. Mod Pathol Off J US Can Acad Pathol Inc 27:644–650 Toon CW, Chou A, DeSilva K, Chan J, Patterson J, Clarkson A, Sioson L, Jankova L, Gill AJ (2014) BRAFV600E immunohistochemistry in conjunction with mismatch repair status predicts survival in patients with colorectal cancer. Mod Pathol Off J US Can Acad Pathol Inc 27:644–650
Zurück zum Zitat Wittekind C, Compton CC, Greene FL, Sobin LH (2002) TNM residual tumor classification revisited. Cancer 94:2511–2516CrossRefPubMed Wittekind C, Compton CC, Greene FL, Sobin LH (2002) TNM residual tumor classification revisited. Cancer 94:2511–2516CrossRefPubMed
Zurück zum Zitat Wu C, Bekaii-Saab T (2012) CpG island methylation, microsatellite instability, and BRAF mutations and their clinical application in the treatment of colon cancer. Chemother Res Pract 2012:359041PubMedPubMedCentral Wu C, Bekaii-Saab T (2012) CpG island methylation, microsatellite instability, and BRAF mutations and their clinical application in the treatment of colon cancer. Chemother Res Pract 2012:359041PubMedPubMedCentral
Zurück zum Zitat Wu M, Semba S, Oue N, Ikehara N, Yasui W, Yokozaki H (2004) BRAF/K-ras mutation, microsatellite instability, and promoter hypermethylation of hMLH1/MGMT in human gastric carcinomas. Gastric Cancer Off J Int Gastric Cancer Assoc Jpn Gastric Cancer Assoc 7:246–253 Wu M, Semba S, Oue N, Ikehara N, Yasui W, Yokozaki H (2004) BRAF/K-ras mutation, microsatellite instability, and promoter hypermethylation of hMLH1/MGMT in human gastric carcinomas. Gastric Cancer Off J Int Gastric Cancer Assoc Jpn Gastric Cancer Assoc 7:246–253
Zurück zum Zitat Yan Y, Grothey A (2015) Molecular profiling in the treatment of colorectal cancer: focus on regorafenib. OncoTargets Ther 8:2949–2957 Yan Y, Grothey A (2015) Molecular profiling in the treatment of colorectal cancer: focus on regorafenib. OncoTargets Ther 8:2949–2957
Zurück zum Zitat Zheng G, Tseng LH, Chen G, Haley L, Illei P, Gocke CD, Eshleman JR, Lin MT (2015) Clinical detection and categorization of uncommon and concomitant mutations involving BRAF. BMC Cancer 15:779CrossRefPubMedPubMedCentral Zheng G, Tseng LH, Chen G, Haley L, Illei P, Gocke CD, Eshleman JR, Lin MT (2015) Clinical detection and categorization of uncommon and concomitant mutations involving BRAF. BMC Cancer 15:779CrossRefPubMedPubMedCentral
Metadaten
Titel
Prognostic value of BRAF V600E mutation and microsatellite instability in Japanese patients with sporadic colorectal cancer
verfasst von
Yu Nakaji
Eiji Oki
Ryota Nakanishi
Koji Ando
Masahiko Sugiyama
Yuichiro Nakashima
Nami Yamashita
Hiroshi Saeki
Yoshinao Oda
Yoshihiko Maehara
Publikationsdatum
26.09.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 1/2017
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-016-2275-4

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