Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAFV600E mutations in colorectal carcinoma

Abstract The activating BRAFV600 mutation is a well-established negative prognostic biomarker in metastatic colorectal carcinoma (CRC). A recently developed monoclonal mouse antibody (clone VE1) has been shown to detect reliably BRAFV600E mutated protein by immunohistochemistry (IHC). In this study,...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Rössle, Matthias [verfasserIn] Sigg, Michèle [verfasserIn] Rüschoff, Jan H. [verfasserIn] Wild, Peter J. [verfasserIn] Moch, Holger [verfasserIn] Weber, Achim [verfasserIn] Rechsteiner, Markus P. [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2013

Schlagwörter:	mutation Immunohistochemistry Sanger sequencing Ultra-deep sequencing Colorectal carcinoma

Übergeordnetes Werk:	Enthalten in: Virchows Archiv - Berlin : Springer, 1847, 463(2013), 5 vom: 02. Okt., Seite 623-631
Übergeordnetes Werk:	volume:463 ; year:2013 ; number:5 ; day:02 ; month:10 ; pages:623-631

Links:	Volltext

DOI / URN:	10.1007/s00428-013-1492-3

Katalog-ID:	SPR005763185

Internformat


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245	1	0	\|a Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAFV600E mutations in colorectal carcinoma
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520			\|a Abstract The activating BRAFV600 mutation is a well-established negative prognostic biomarker in metastatic colorectal carcinoma (CRC). A recently developed monoclonal mouse antibody (clone VE1) has been shown to detect reliably BRAFV600E mutated protein by immunohistochemistry (IHC). In this study, we aimed to compare the detection of BRAFV600E mutations by IHC, Sanger sequencing (SaS), and ultra-deep sequencing (UDS) in CRC. VE1-IHC was established in a cohort of 68 KRAS wild-type CRCs. The VE1-IHC was only positive in the three patients with a known BRAFV600E mutation as assessed by SaS and UDS. The test cohort consisted of 265 non-selected, consecutive CRC samples. Thirty-nine out of 265 cases (14.7 %) were positive by VE1-IHC. SaS of 20 randomly selected IHC negative tumors showed BRAF wild-type (20/20). Twenty-four IHC-positive cases were confirmed by SaS (24/39; 61.5 %) and 15 IHC-positive cases (15/39; 38.5 %) showed a BRAF wild-type by SaS. UDS detected a BRAFV600E mutation in 13 of these 15 discordant cases. In one tumor, the mutation frequency was below our threshold for UDS positivity, while in another case, UDS could not be performed due to low DNA amount. Statistical analysis showed sensitivities of 100 % and 63 % and specificities of 95 and 100 % for VE1-IHC and SaS, respectively, compared to combined results of SaS and UDS. Our data suggests that there is high concordance between UDS and IHC using the anti-$ BRAF^{V600E} $ (VE1) antibody. Thus, VE1 immunohistochemistry is a highly sensitive and specific method in detecting BRAFV600E mutations in colorectal carcinoma.
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700	1		\|a Weber, Achim \|e verfasserin \|4 aut
700	1		\|a Rechsteiner, Markus P. \|e verfasserin \|4 aut
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matchkey_str	article:14322307:2013----::lrdesqecncnimimnhsohmsraaihyestvadpcfcehdodtcigrf
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publishDate	2013
allfields	10.1007/s00428-013-1492-3 doi (DE-627)SPR005763185 (SPR)s00428-013-1492-3-e DE-627 ger DE-627 rakwb eng 610 ASE 44.47 bkl Rössle, Matthias verfasserin aut Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAFV600E mutations in colorectal carcinoma 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The activating BRAFV600 mutation is a well-established negative prognostic biomarker in metastatic colorectal carcinoma (CRC). A recently developed monoclonal mouse antibody (clone VE1) has been shown to detect reliably BRAFV600E mutated protein by immunohistochemistry (IHC). In this study, we aimed to compare the detection of BRAFV600E mutations by IHC, Sanger sequencing (SaS), and ultra-deep sequencing (UDS) in CRC. VE1-IHC was established in a cohort of 68 KRAS wild-type CRCs. The VE1-IHC was only positive in the three patients with a known BRAFV600E mutation as assessed by SaS and UDS. The test cohort consisted of 265 non-selected, consecutive CRC samples. Thirty-nine out of 265 cases (14.7 %) were positive by VE1-IHC. SaS of 20 randomly selected IHC negative tumors showed BRAF wild-type (20/20). Twenty-four IHC-positive cases were confirmed by SaS (24/39; 61.5 %) and 15 IHC-positive cases (15/39; 38.5 %) showed a BRAF wild-type by SaS. UDS detected a BRAFV600E mutation in 13 of these 15 discordant cases. In one tumor, the mutation frequency was below our threshold for UDS positivity, while in another case, UDS could not be performed due to low DNA amount. Statistical analysis showed sensitivities of 100 % and 63 % and specificities of 95 and 100 % for VE1-IHC and SaS, respectively, compared to combined results of SaS and UDS. Our data suggests that there is high concordance between UDS and IHC using the anti-$ BRAF^{V600E} $ (VE1) antibody. Thus, VE1 immunohistochemistry is a highly sensitive and specific method in detecting BRAFV600E mutations in colorectal carcinoma. mutation (dpeaa)DE-He213 Immunohistochemistry (dpeaa)DE-He213 Sanger sequencing (dpeaa)DE-He213 Ultra-deep sequencing (dpeaa)DE-He213 Colorectal carcinoma (dpeaa)DE-He213 Sigg, Michèle verfasserin aut Rüschoff, Jan H. verfasserin aut Wild, Peter J. verfasserin aut Moch, Holger verfasserin aut Weber, Achim verfasserin aut Rechsteiner, Markus P. verfasserin aut Enthalten in Virchows Archiv Berlin : Springer, 1847 463(2013), 5 vom: 02. Okt., Seite 623-631 (DE-627)254910645 (DE-600)1463276-7 1432-2307 nnns volume:463 year:2013 number:5 day:02 month:10 pages:623-631 https://dx.doi.org/10.1007/s00428-013-1492-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.47 ASE AR 463 2013 5 02 10 623-631
spelling	10.1007/s00428-013-1492-3 doi (DE-627)SPR005763185 (SPR)s00428-013-1492-3-e DE-627 ger DE-627 rakwb eng 610 ASE 44.47 bkl Rössle, Matthias verfasserin aut Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAFV600E mutations in colorectal carcinoma 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The activating BRAFV600 mutation is a well-established negative prognostic biomarker in metastatic colorectal carcinoma (CRC). A recently developed monoclonal mouse antibody (clone VE1) has been shown to detect reliably BRAFV600E mutated protein by immunohistochemistry (IHC). In this study, we aimed to compare the detection of BRAFV600E mutations by IHC, Sanger sequencing (SaS), and ultra-deep sequencing (UDS) in CRC. VE1-IHC was established in a cohort of 68 KRAS wild-type CRCs. The VE1-IHC was only positive in the three patients with a known BRAFV600E mutation as assessed by SaS and UDS. The test cohort consisted of 265 non-selected, consecutive CRC samples. Thirty-nine out of 265 cases (14.7 %) were positive by VE1-IHC. SaS of 20 randomly selected IHC negative tumors showed BRAF wild-type (20/20). Twenty-four IHC-positive cases were confirmed by SaS (24/39; 61.5 %) and 15 IHC-positive cases (15/39; 38.5 %) showed a BRAF wild-type by SaS. UDS detected a BRAFV600E mutation in 13 of these 15 discordant cases. In one tumor, the mutation frequency was below our threshold for UDS positivity, while in another case, UDS could not be performed due to low DNA amount. Statistical analysis showed sensitivities of 100 % and 63 % and specificities of 95 and 100 % for VE1-IHC and SaS, respectively, compared to combined results of SaS and UDS. Our data suggests that there is high concordance between UDS and IHC using the anti-$ BRAF^{V600E} $ (VE1) antibody. Thus, VE1 immunohistochemistry is a highly sensitive and specific method in detecting BRAFV600E mutations in colorectal carcinoma. mutation (dpeaa)DE-He213 Immunohistochemistry (dpeaa)DE-He213 Sanger sequencing (dpeaa)DE-He213 Ultra-deep sequencing (dpeaa)DE-He213 Colorectal carcinoma (dpeaa)DE-He213 Sigg, Michèle verfasserin aut Rüschoff, Jan H. verfasserin aut Wild, Peter J. verfasserin aut Moch, Holger verfasserin aut Weber, Achim verfasserin aut Rechsteiner, Markus P. verfasserin aut Enthalten in Virchows Archiv Berlin : Springer, 1847 463(2013), 5 vom: 02. Okt., Seite 623-631 (DE-627)254910645 (DE-600)1463276-7 1432-2307 nnns volume:463 year:2013 number:5 day:02 month:10 pages:623-631 https://dx.doi.org/10.1007/s00428-013-1492-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.47 ASE AR 463 2013 5 02 10 623-631
allfields_unstemmed	10.1007/s00428-013-1492-3 doi (DE-627)SPR005763185 (SPR)s00428-013-1492-3-e DE-627 ger DE-627 rakwb eng 610 ASE 44.47 bkl Rössle, Matthias verfasserin aut Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAFV600E mutations in colorectal carcinoma 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The activating BRAFV600 mutation is a well-established negative prognostic biomarker in metastatic colorectal carcinoma (CRC). A recently developed monoclonal mouse antibody (clone VE1) has been shown to detect reliably BRAFV600E mutated protein by immunohistochemistry (IHC). In this study, we aimed to compare the detection of BRAFV600E mutations by IHC, Sanger sequencing (SaS), and ultra-deep sequencing (UDS) in CRC. VE1-IHC was established in a cohort of 68 KRAS wild-type CRCs. The VE1-IHC was only positive in the three patients with a known BRAFV600E mutation as assessed by SaS and UDS. The test cohort consisted of 265 non-selected, consecutive CRC samples. Thirty-nine out of 265 cases (14.7 %) were positive by VE1-IHC. SaS of 20 randomly selected IHC negative tumors showed BRAF wild-type (20/20). Twenty-four IHC-positive cases were confirmed by SaS (24/39; 61.5 %) and 15 IHC-positive cases (15/39; 38.5 %) showed a BRAF wild-type by SaS. UDS detected a BRAFV600E mutation in 13 of these 15 discordant cases. In one tumor, the mutation frequency was below our threshold for UDS positivity, while in another case, UDS could not be performed due to low DNA amount. Statistical analysis showed sensitivities of 100 % and 63 % and specificities of 95 and 100 % for VE1-IHC and SaS, respectively, compared to combined results of SaS and UDS. Our data suggests that there is high concordance between UDS and IHC using the anti-$ BRAF^{V600E} $ (VE1) antibody. Thus, VE1 immunohistochemistry is a highly sensitive and specific method in detecting BRAFV600E mutations in colorectal carcinoma. mutation (dpeaa)DE-He213 Immunohistochemistry (dpeaa)DE-He213 Sanger sequencing (dpeaa)DE-He213 Ultra-deep sequencing (dpeaa)DE-He213 Colorectal carcinoma (dpeaa)DE-He213 Sigg, Michèle verfasserin aut Rüschoff, Jan H. verfasserin aut Wild, Peter J. verfasserin aut Moch, Holger verfasserin aut Weber, Achim verfasserin aut Rechsteiner, Markus P. verfasserin aut Enthalten in Virchows Archiv Berlin : Springer, 1847 463(2013), 5 vom: 02. Okt., Seite 623-631 (DE-627)254910645 (DE-600)1463276-7 1432-2307 nnns volume:463 year:2013 number:5 day:02 month:10 pages:623-631 https://dx.doi.org/10.1007/s00428-013-1492-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.47 ASE AR 463 2013 5 02 10 623-631
allfieldsGer	10.1007/s00428-013-1492-3 doi (DE-627)SPR005763185 (SPR)s00428-013-1492-3-e DE-627 ger DE-627 rakwb eng 610 ASE 44.47 bkl Rössle, Matthias verfasserin aut Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAFV600E mutations in colorectal carcinoma 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The activating BRAFV600 mutation is a well-established negative prognostic biomarker in metastatic colorectal carcinoma (CRC). A recently developed monoclonal mouse antibody (clone VE1) has been shown to detect reliably BRAFV600E mutated protein by immunohistochemistry (IHC). In this study, we aimed to compare the detection of BRAFV600E mutations by IHC, Sanger sequencing (SaS), and ultra-deep sequencing (UDS) in CRC. VE1-IHC was established in a cohort of 68 KRAS wild-type CRCs. The VE1-IHC was only positive in the three patients with a known BRAFV600E mutation as assessed by SaS and UDS. The test cohort consisted of 265 non-selected, consecutive CRC samples. Thirty-nine out of 265 cases (14.7 %) were positive by VE1-IHC. SaS of 20 randomly selected IHC negative tumors showed BRAF wild-type (20/20). Twenty-four IHC-positive cases were confirmed by SaS (24/39; 61.5 %) and 15 IHC-positive cases (15/39; 38.5 %) showed a BRAF wild-type by SaS. UDS detected a BRAFV600E mutation in 13 of these 15 discordant cases. In one tumor, the mutation frequency was below our threshold for UDS positivity, while in another case, UDS could not be performed due to low DNA amount. Statistical analysis showed sensitivities of 100 % and 63 % and specificities of 95 and 100 % for VE1-IHC and SaS, respectively, compared to combined results of SaS and UDS. Our data suggests that there is high concordance between UDS and IHC using the anti-$ BRAF^{V600E} $ (VE1) antibody. Thus, VE1 immunohistochemistry is a highly sensitive and specific method in detecting BRAFV600E mutations in colorectal carcinoma. mutation (dpeaa)DE-He213 Immunohistochemistry (dpeaa)DE-He213 Sanger sequencing (dpeaa)DE-He213 Ultra-deep sequencing (dpeaa)DE-He213 Colorectal carcinoma (dpeaa)DE-He213 Sigg, Michèle verfasserin aut Rüschoff, Jan H. verfasserin aut Wild, Peter J. verfasserin aut Moch, Holger verfasserin aut Weber, Achim verfasserin aut Rechsteiner, Markus P. verfasserin aut Enthalten in Virchows Archiv Berlin : Springer, 1847 463(2013), 5 vom: 02. Okt., Seite 623-631 (DE-627)254910645 (DE-600)1463276-7 1432-2307 nnns volume:463 year:2013 number:5 day:02 month:10 pages:623-631 https://dx.doi.org/10.1007/s00428-013-1492-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.47 ASE AR 463 2013 5 02 10 623-631
allfieldsSound	10.1007/s00428-013-1492-3 doi (DE-627)SPR005763185 (SPR)s00428-013-1492-3-e DE-627 ger DE-627 rakwb eng 610 ASE 44.47 bkl Rössle, Matthias verfasserin aut Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAFV600E mutations in colorectal carcinoma 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The activating BRAFV600 mutation is a well-established negative prognostic biomarker in metastatic colorectal carcinoma (CRC). A recently developed monoclonal mouse antibody (clone VE1) has been shown to detect reliably BRAFV600E mutated protein by immunohistochemistry (IHC). In this study, we aimed to compare the detection of BRAFV600E mutations by IHC, Sanger sequencing (SaS), and ultra-deep sequencing (UDS) in CRC. VE1-IHC was established in a cohort of 68 KRAS wild-type CRCs. The VE1-IHC was only positive in the three patients with a known BRAFV600E mutation as assessed by SaS and UDS. The test cohort consisted of 265 non-selected, consecutive CRC samples. Thirty-nine out of 265 cases (14.7 %) were positive by VE1-IHC. SaS of 20 randomly selected IHC negative tumors showed BRAF wild-type (20/20). Twenty-four IHC-positive cases were confirmed by SaS (24/39; 61.5 %) and 15 IHC-positive cases (15/39; 38.5 %) showed a BRAF wild-type by SaS. UDS detected a BRAFV600E mutation in 13 of these 15 discordant cases. In one tumor, the mutation frequency was below our threshold for UDS positivity, while in another case, UDS could not be performed due to low DNA amount. Statistical analysis showed sensitivities of 100 % and 63 % and specificities of 95 and 100 % for VE1-IHC and SaS, respectively, compared to combined results of SaS and UDS. Our data suggests that there is high concordance between UDS and IHC using the anti-$ BRAF^{V600E} $ (VE1) antibody. Thus, VE1 immunohistochemistry is a highly sensitive and specific method in detecting BRAFV600E mutations in colorectal carcinoma. mutation (dpeaa)DE-He213 Immunohistochemistry (dpeaa)DE-He213 Sanger sequencing (dpeaa)DE-He213 Ultra-deep sequencing (dpeaa)DE-He213 Colorectal carcinoma (dpeaa)DE-He213 Sigg, Michèle verfasserin aut Rüschoff, Jan H. verfasserin aut Wild, Peter J. verfasserin aut Moch, Holger verfasserin aut Weber, Achim verfasserin aut Rechsteiner, Markus P. verfasserin aut Enthalten in Virchows Archiv Berlin : Springer, 1847 463(2013), 5 vom: 02. Okt., Seite 623-631 (DE-627)254910645 (DE-600)1463276-7 1432-2307 nnns volume:463 year:2013 number:5 day:02 month:10 pages:623-631 https://dx.doi.org/10.1007/s00428-013-1492-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.47 ASE AR 463 2013 5 02 10 623-631
language	English
source	Enthalten in Virchows Archiv 463(2013), 5 vom: 02. Okt., Seite 623-631 volume:463 year:2013 number:5 day:02 month:10 pages:623-631
sourceStr	Enthalten in Virchows Archiv 463(2013), 5 vom: 02. Okt., Seite 623-631 volume:463 year:2013 number:5 day:02 month:10 pages:623-631
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	mutation Immunohistochemistry Sanger sequencing Ultra-deep sequencing Colorectal carcinoma
dewey-raw	610
isfreeaccess_bool	false
container_title	Virchows Archiv
authorswithroles_txt_mv	Rössle, Matthias @@aut@@ Sigg, Michèle @@aut@@ Rüschoff, Jan H. @@aut@@ Wild, Peter J. @@aut@@ Moch, Holger @@aut@@ Weber, Achim @@aut@@ Rechsteiner, Markus P. @@aut@@
publishDateDaySort_date	2013-10-02T00:00:00Z
hierarchy_top_id	254910645
dewey-sort	3610
id	SPR005763185
language_de	englisch
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author	Rössle, Matthias
spellingShingle	Rössle, Matthias ddc 610 bkl 44.47 misc mutation misc Immunohistochemistry misc Sanger sequencing misc Ultra-deep sequencing misc Colorectal carcinoma Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAFV600E mutations in colorectal carcinoma
authorStr	Rössle, Matthias
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topic_title	610 ASE 44.47 bkl Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAFV600E mutations in colorectal carcinoma mutation (dpeaa)DE-He213 Immunohistochemistry (dpeaa)DE-He213 Sanger sequencing (dpeaa)DE-He213 Ultra-deep sequencing (dpeaa)DE-He213 Colorectal carcinoma (dpeaa)DE-He213
topic	ddc 610 bkl 44.47 misc mutation misc Immunohistochemistry misc Sanger sequencing misc Ultra-deep sequencing misc Colorectal carcinoma
topic_unstemmed	ddc 610 bkl 44.47 misc mutation misc Immunohistochemistry misc Sanger sequencing misc Ultra-deep sequencing misc Colorectal carcinoma
topic_browse	ddc 610 bkl 44.47 misc mutation misc Immunohistochemistry misc Sanger sequencing misc Ultra-deep sequencing misc Colorectal carcinoma
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title	Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAFV600E mutations in colorectal carcinoma
ctrlnum	(DE-627)SPR005763185 (SPR)s00428-013-1492-3-e
title_full	Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAFV600E mutations in colorectal carcinoma
author_sort	Rössle, Matthias
journal	Virchows Archiv
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author_browse	Rössle, Matthias Sigg, Michèle Rüschoff, Jan H. Wild, Peter J. Moch, Holger Weber, Achim Rechsteiner, Markus P.
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title_sort	ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting brafv600e mutations in colorectal carcinoma
title_auth	Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAFV600E mutations in colorectal carcinoma
abstract	Abstract The activating BRAFV600 mutation is a well-established negative prognostic biomarker in metastatic colorectal carcinoma (CRC). A recently developed monoclonal mouse antibody (clone VE1) has been shown to detect reliably BRAFV600E mutated protein by immunohistochemistry (IHC). In this study, we aimed to compare the detection of BRAFV600E mutations by IHC, Sanger sequencing (SaS), and ultra-deep sequencing (UDS) in CRC. VE1-IHC was established in a cohort of 68 KRAS wild-type CRCs. The VE1-IHC was only positive in the three patients with a known BRAFV600E mutation as assessed by SaS and UDS. The test cohort consisted of 265 non-selected, consecutive CRC samples. Thirty-nine out of 265 cases (14.7 %) were positive by VE1-IHC. SaS of 20 randomly selected IHC negative tumors showed BRAF wild-type (20/20). Twenty-four IHC-positive cases were confirmed by SaS (24/39; 61.5 %) and 15 IHC-positive cases (15/39; 38.5 %) showed a BRAF wild-type by SaS. UDS detected a BRAFV600E mutation in 13 of these 15 discordant cases. In one tumor, the mutation frequency was below our threshold for UDS positivity, while in another case, UDS could not be performed due to low DNA amount. Statistical analysis showed sensitivities of 100 % and 63 % and specificities of 95 and 100 % for VE1-IHC and SaS, respectively, compared to combined results of SaS and UDS. Our data suggests that there is high concordance between UDS and IHC using the anti-$ BRAF^{V600E} $ (VE1) antibody. Thus, VE1 immunohistochemistry is a highly sensitive and specific method in detecting BRAFV600E mutations in colorectal carcinoma.
abstractGer	Abstract The activating BRAFV600 mutation is a well-established negative prognostic biomarker in metastatic colorectal carcinoma (CRC). A recently developed monoclonal mouse antibody (clone VE1) has been shown to detect reliably BRAFV600E mutated protein by immunohistochemistry (IHC). In this study, we aimed to compare the detection of BRAFV600E mutations by IHC, Sanger sequencing (SaS), and ultra-deep sequencing (UDS) in CRC. VE1-IHC was established in a cohort of 68 KRAS wild-type CRCs. The VE1-IHC was only positive in the three patients with a known BRAFV600E mutation as assessed by SaS and UDS. The test cohort consisted of 265 non-selected, consecutive CRC samples. Thirty-nine out of 265 cases (14.7 %) were positive by VE1-IHC. SaS of 20 randomly selected IHC negative tumors showed BRAF wild-type (20/20). Twenty-four IHC-positive cases were confirmed by SaS (24/39; 61.5 %) and 15 IHC-positive cases (15/39; 38.5 %) showed a BRAF wild-type by SaS. UDS detected a BRAFV600E mutation in 13 of these 15 discordant cases. In one tumor, the mutation frequency was below our threshold for UDS positivity, while in another case, UDS could not be performed due to low DNA amount. Statistical analysis showed sensitivities of 100 % and 63 % and specificities of 95 and 100 % for VE1-IHC and SaS, respectively, compared to combined results of SaS and UDS. Our data suggests that there is high concordance between UDS and IHC using the anti-$ BRAF^{V600E} $ (VE1) antibody. Thus, VE1 immunohistochemistry is a highly sensitive and specific method in detecting BRAFV600E mutations in colorectal carcinoma.
abstract_unstemmed	Abstract The activating BRAFV600 mutation is a well-established negative prognostic biomarker in metastatic colorectal carcinoma (CRC). A recently developed monoclonal mouse antibody (clone VE1) has been shown to detect reliably BRAFV600E mutated protein by immunohistochemistry (IHC). In this study, we aimed to compare the detection of BRAFV600E mutations by IHC, Sanger sequencing (SaS), and ultra-deep sequencing (UDS) in CRC. VE1-IHC was established in a cohort of 68 KRAS wild-type CRCs. The VE1-IHC was only positive in the three patients with a known BRAFV600E mutation as assessed by SaS and UDS. The test cohort consisted of 265 non-selected, consecutive CRC samples. Thirty-nine out of 265 cases (14.7 %) were positive by VE1-IHC. SaS of 20 randomly selected IHC negative tumors showed BRAF wild-type (20/20). Twenty-four IHC-positive cases were confirmed by SaS (24/39; 61.5 %) and 15 IHC-positive cases (15/39; 38.5 %) showed a BRAF wild-type by SaS. UDS detected a BRAFV600E mutation in 13 of these 15 discordant cases. In one tumor, the mutation frequency was below our threshold for UDS positivity, while in another case, UDS could not be performed due to low DNA amount. Statistical analysis showed sensitivities of 100 % and 63 % and specificities of 95 and 100 % for VE1-IHC and SaS, respectively, compared to combined results of SaS and UDS. Our data suggests that there is high concordance between UDS and IHC using the anti-$ BRAF^{V600E} $ (VE1) antibody. Thus, VE1 immunohistochemistry is a highly sensitive and specific method in detecting BRAFV600E mutations in colorectal carcinoma.
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container_issue	5
title_short	Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAFV600E mutations in colorectal carcinoma
url	https://dx.doi.org/10.1007/s00428-013-1492-3
remote_bool	true
author2	Sigg, Michèle Rüschoff, Jan H. Wild, Peter J. Moch, Holger Weber, Achim Rechsteiner, Markus P.
author2Str	Sigg, Michèle Rüschoff, Jan H. Wild, Peter J. Moch, Holger Weber, Achim Rechsteiner, Markus P.
ppnlink	254910645
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isOA_txt	false
hochschulschrift_bool	false
doi_str	10.1007/s00428-013-1492-3
up_date	2024-07-03T18:31:38.755Z
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Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAFV600E mutations in colorectal carcinoma

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