Detection of BRAF V600E mutations in skin metastases of malignant melanoma by monoclonal antibody VE1

Skorokhod, Alexander; Capper, David; Deimling, Andreas von; Enk, Alexander H.; Helmbold, Peter

doi:10.1016/j.jaad.2012.03.022

Cited by 40 publications

(49 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, IHC was able to detect more specimens harboring BRAF V600E mutations compared with the cobas test. The high efficiency of IHC described in our study is consistent with other groups that previously reported the high sensitivity and specificity of the anti-BRAF V600E VE1 antibody (Marin et al, 2014;Skorokhod et al, 2012;Colomba et al, 2013;Chen et al, 2014).…”

Section: Discussionsupporting

confidence: 92%

See 1 more Smart Citation

Intra- and Inter-Tumoral Homogeneity of BRAF V600E Mutations in Melanoma Tumors

Riveiro-Falkenbach

Villanueva

Garrido

et al. 2015

Journal of Investigative Dermatology

View full text Add to dashboard Cite

The era of targeted therapy has introduced a new therapeutic perspective for melanoma patients. Treatment with BRAFV600 inhibitors has improved overall and disease-free survival in metastatic melanoma patients whose tumors harbor BRAFV600 mutations. Although the BRAFV600E mutation appears to have a critical role in tumor initiation, its expression during tumor progression remains controversial. In fact, various authors claim that BRAFV600E heterogeneity is evident in melanoma tumors. Herein, we investigated the pattern of BRAFV600E expression in matched primary and metastatic samples from 140 patients. Using a combination of real-time PCR and immunohistochemical analyses, we demonstrated that BRAFV600E expression is homogeneous in melanoma tumors and hypothesized that the heterogeneity described by others might be attributable to technical issues when molecular methods are used. We also demonstrated the high efficiency of the anti-BRAFV600E VE1 antibody for the detection of BRAFV600E mutations in melanoma tumors.

show abstract

Section: Discussionsupporting

confidence: 92%

“…Recently, a monoclonal antibody against BRAF V600E has been developed to detect this mutated protein in tumor paraffin sections (Capper et al, 2011). Studies of melanoma tumors that harbor the BRAF V600E mutation revealed high antibody sensitivity and specificity Skorokhod et al, 2012;Colomba et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Intra- and Inter-Tumoral Homogeneity of BRAF V600E Mutations in Melanoma Tumors

Riveiro-Falkenbach

Villanueva

Garrido

et al. 2015

Journal of Investigative Dermatology

View full text Add to dashboard Cite

show abstract

“…33,34 Implementation of VE1 immunohistochemistry for the prediction of a BRAF V600E mutation has been investigated by various groups and for various types of cancer. [15][16][17][18][19][20][21][23][24][25] VE1 immunohistochemistry has the advantage of being rapid and relatively inexpensive, while the sensitivity and specificity are comparable to DNA-based methods. For pathologists, an additional well-appreciated advantage is the in situ mutation detection that provides information on the mutated cell population, as well as an additional visual sample verification that a faceless DNA sample does not offer.…”

Section: Discussionmentioning

confidence: 99%

“…38 In single instances, other rare BRAF mutations were detected (eg, BRAF K601E) for which data on potential clinical activity of BRAF inhibitors are not available. VE1 immunohistochemistry does not detect V600K, V600D, or other rare mutations, 15,16 and would thus fail to identify these potential candidates for targeted therapy. In our collection of 42 VE1-negative intrahepatic cholangiocarcinomas, we did not observe any non-V600E mutations, indicating that they altogether likely represent rare events in intrahepatic cholangiocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…2 In this study, we investigated a large collection of biliary tract cancers for BRAF V600E mutations using a novel mutation-specific antibody (clone VE1) that specifically binds to BRAF V600E-mutated protein that is in general located in the cytoplasm. VE1 immunohistochemistry has proven to be highly sensitive and specific for various tumor types, including melanoma, [15][16][17][18][19] thyroid carcinoma, 20,21 colorectal carcinoma, 22,23 ganglioglioma, 24 and hairy cell leukemia, 25 among others.…”

mentioning

confidence: 99%

See 1 more Smart Citation

BRAF V600E-specific immunohistochemistry reveals low mutation rates in biliary tract cancer and restriction to intrahepatic cholangiocarcinoma

et al. 2014

Self Cite

View full text Add to dashboard Cite

BRAF mutations have emerged as an important predictive biomarker for metastasized melanoma. Other types of cancer may also benefit from BRAF mutation-targeted therapies. In biliary tract cancer, reported BRAF mutation rates are highly controversial, ranging from 0 to 33% in adenocarcinoma of the gallbladder and 0 to 22% in cholangiocarcinoma. We here analyzed tissue microarrays of a large cohort of biliary tract cancer (n ¼ 377) including 159 intrahepatic cholangiocarcinomas, 149 extrahepatic cholangiocarcinomas, and 69 adenocarcinomas of the gallbladder for BRAF V600E mutation using a highly sensitive immunohistochemical screening approach implementing the BRAF V600E protein-specific antibody VE1. All VE1-positive cases as well as 42 VE1-negative cases were additionally analyzed by Sanger sequencing. In total, only 5 VE1-positive cases were detected (5/377; 1%). BRAF V600E mutation was confirmed by direct sequencing in all cases. All 5 mutated cases were intrahepatic cholangiocarcinomas (5/159; 3%). None of the extrahepatic cholangiocarcinomas and adenocarcinomas of the gallbladder were VE1 positive. Apart from the subtype restriction of BRAF V600E mutation to intrahepatic cholangiocarcinoma and a female predominance (4 female, 1 male), no significant correlation with clinicopathological data and patient outcome was detected. In conclusion, we demonstrate that BRAF V600E mutation is a rare event in biliary tract cancer, accounting for only 1% of all subtypes, and is restricted to intrahepatic cholangiocarcinoma. In addition, we demonstrate that VE1 immunohistochemistry is a feasible approach to routinely screen for BRAF V600E mutation in biliary tract cancer patients, thereby facilitating the detection of rare patients who may benefit from BRAF mutation-targeted therapies.

show abstract

BRAF^V600EProtein Expression in Primary Cutaneous Malignant Melanomas and Paired Metastases

et al. 2015

View full text Add to dashboard Cite

We found VE1 immunohistochemical analysis to be a useful and rapid assay for BRAFV600E mutations that may contribute to the detection of intratumoral and intertumoral heterogenetic subclones. Tumors with positive results, including strong staining, should be expedited for confirmatory BRAF mutation testing. If this test result is negative, a false-negative result of the mutation analysis should be considered. Validation of VE1 immunohistochemical analysis in clinical practice is needed.

show abstract

Detection of BRAF V600E mutations in skin metastases of malignant melanoma by monoclonal antibody VE1

Cited by 40 publications

References 5 publications

Intra- and Inter-Tumoral Homogeneity of BRAF V600E Mutations in Melanoma Tumors

Intra- and Inter-Tumoral Homogeneity of BRAF V600E Mutations in Melanoma Tumors

BRAF V600E-specific immunohistochemistry reveals low mutation rates in biliary tract cancer and restriction to intrahepatic cholangiocarcinoma

BRAF^V600EProtein Expression in Primary Cutaneous Malignant Melanomas and Paired Metastases

Contact Info

Product

Resources

About

Detection of BRAF V600E mutations in skin metastases of malignant melanoma by monoclonal antibody VE1

Cited by 40 publications

References 5 publications

Intra- and Inter-Tumoral Homogeneity of BRAF V600E Mutations in Melanoma Tumors

Intra- and Inter-Tumoral Homogeneity of BRAF V600E Mutations in Melanoma Tumors

BRAF V600E-specific immunohistochemistry reveals low mutation rates in biliary tract cancer and restriction to intrahepatic cholangiocarcinoma

BRAFV600EProtein Expression in Primary Cutaneous Malignant Melanomas and Paired Metastases

Contact Info

Product

Resources

About

BRAF^V600EProtein Expression in Primary Cutaneous Malignant Melanomas and Paired Metastases