Concordance in <scp>BRAF</scp> V600E status over time in malignant melanoma and corresponding metastases

Nielsen, Line B; Dabrosin, Nina; Sloth, Karen; Bønnelykke-Behrndtz, Marie Louise; Steiniche, Torben; Lade-Keller, Johanne

doi:10.1111/his.13431

Cited by 11 publications

(22 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While the finding of 100% concordance may not be replicated in future larger series or in other populations, taken in the context of previous studies our findings add further support to the conclusion that differences in BRAF status between primary and metastatic sites as determined by IHC are significantly less common than discordance as assessed by PCR. [18][19][20][21][22][23][24]37 Our description of a case of apparent PCR discordance which was subsequently shown to be due to a false negative at one site suggests that some of this difference in findings between methods may be due to technical difficulties with obtaining accurate molecular data from small tumor deposits.…”

Section: Discussionmentioning

confidence: 88%

“…It is noteworthy that in previous work on BRAF status discordance between primary and metastatic melanoma, the pooled rate of discordance was lower in studies using IHC to detect mutant protein, compared with those using DNA‐based approaches . Across seven studies using the VE1 anti‐V600E BRAF antibody, the mean discordance was 5.6% . By contrast, the mean discordance was 14% in DNA‐based studies .…”

Section: Introductionmentioning

confidence: 84%

“…Menzies et al and Manfredi et al reported that BRAF status of melanoma metastases as assessed by IHC were identical to that of the matched primary in all cases in series of 64 and 54 patients, respectively . A very recent study by Nielsen et al included 82 patients with primary and metastatic melanoma with all but one case concordant . The largest study to use IHC to compare BRAF status between primary melanomas and their metastases was Boursault et al, which included 88 patients and reported discordance in 4.5% .…”

Section: Discussionmentioning

confidence: 99%

“…16 Across seven studies using the VE1 anti-V600E BRAF antibody, the mean discordance was 5.6%. [18][19][20][21][22][23][24] By contrast, the mean discordance was 14% in DNA-based studies. 16 The reasons for this difference remain obscure and could include technical issues around use of the relatively recently developed VE1 antibody.…”

Section: Introductionmentioning

confidence: 90%

See 3 more Smart Citations

High concordance of BRAF mutational status in matched primary and metastatic melanoma

et al. 2018

View full text Add to dashboard Cite

Background Techniques for the accurate identification of activating mutations of BRAF in metastatic melanoma are of great clinical importance, due to the availability of targeted therapies for these tumors. There is uncertainty regarding the frequency with which BRAF status differs between primary and metastatic sites. Methods Between 2011 and 2016, 219 melanoma cases underwent BRAF testing in our institution. In 53 of these cases, paired primary and metastatic specimens were available for polymerase chain reaction (PCR) and immunohistochemical evaluation. Results Fifty‐two out of 53 cases (98%) showed concordant BRAF status between primary and metastatic site by immunohistochemistry (IHC). In one case, a metastasis and its matched primary were positive by IHC, but the metastasis was negative on PCR. On further investigation, PCR was positive in the primary, and repeat PCR in the metastasis was positive, following macrodissection. Conclusions Our results suggest that discordance of BRAF mutational status between primaries and metastases is a rare occurrence. In one case, IHC provided strong evidence that initial PCR testing had provided a false‐negative result due to low tumor volume. Thus, in cases where tissue is difficult to obtain from a metastasis or unavailable, the primary tumor can be used with confidence.

show abstract

Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

See 2 more Smart Citations

High concordance of BRAF mutational status in matched primary and metastatic melanoma

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In the context of our mutation prediction model, primary melanomas could be rapidly screened on initial H&E slides. While we did not utilize metastatic melanoma samples in this study over concerns of suboptimal training on a smaller dataset, a number of studies demonstrate mutational testing on the primary tumor is an acceptable alternative 38, 39, 40 . Our BRAF model could potentially be used in conjunction with IHC screening, where concordant cases do not require confirmatory sequencing.…”

Section: Discussionmentioning

confidence: 99%

A Deep Learning Approach for Rapid Mutational Screening in Melanoma

Kim

Nomikou

Coudray³

et al. 2019

Preprint

View full text Add to dashboard Cite

36DNA-based molecular assays for determining mutational status in melanomas are time-37 consuming and costly. As an alternative, we applied a deep convolutional neural network 38 (CNN) to histopathology images of tumors from 257 melanoma patients and developed a 39 fully automated model that first selects for tumor-rich areas (Area under the curve 40 AUC=0.98), and second, predicts for the presence of mutated BRAF or NRAS. Network 41 performance was enhanced on BRAF-mutated melanomas 1.0 mm (AUC=0.83) and on 42 non-ulcerated NRAS-mutated melanomas (AUC=0.92). Applying our models to 43 histological images of primary melanomas from The Cancer Genome Atlas database also 44 demonstrated improved performances on thinner BRAF-mutated melanomas and non-45 ulcerated NRAS-mutated melanomas. We propose that deep learning-based analysis of 46 histological images has the potential to become integrated into clinical decision making 47 for the rapid detection of mutations of interest in melanoma. 48 49 50 Mutations in the BRAF oncogene are found in 50-60% of all melanomas 1 , while NRAS 51 mutations comprise an additional 15-20%. With the development of targeted therapies 2, 52 3 , determining the mutational status of BRAF and NRAS has become an integral 53 component for the management of Stage III/IV melanomas. DNA molecular assays such 54 as Sanger sequencing, pyrosequencing, and next generation sequencing (NGS) are the 55 current gold standard to determine mutational status 4 . However, these methods are costly 56 and time-consuming. Immunohistochemistry, real-time polymerase chain reaction (PCR), 57 and automated platforms 5, 6, 7 are rapid and less expensive alternatives, but are limited to 58 screening for specific mutations, such as BRAF-V600E/K or NRAS-Q61R/L, and may 59 potentially fail to identify rare mutational variants in patients that might have otherwise 60 benefited from adjuvant targeted therapy.61 62 Deep Convolutional Neural Network (CNN) methods to predict mutational status have 63 been demonstrated in other solid tumors. CNNs utilize multiple layers of convolution 64 operations, pooling layers, and fully connected layers to perform classification of images 65 to classes of interest through identification of various image features often not directly 66 detectable by the human eye. Deep CNNs, which utilize non-linear learning algorithms, 67have been successful in manipulating and processing large data sets, particularly for 68 image analysis 8 . Using images from The Cancer Genome Atlas (TCGA), a collaborative 69 cancer genomics database 9 , our group has previously developed a machine learning 70 algorithm that can predict for 6 different genes, including EGFR and STK11, in lung 71 carcinoma 10 . In breast cancer, deep learning applied to tumor microarray images has 72 been shown to predict for ER status with an 84% accuracy 11 . 73 74 In this study, we adapt our previous deep learning algorithm to a different dataset 75 comprised of histopathology images of primary melanomas resected from patients 76 pros...

show abstract

Skin

Ferringer

2022

Handbook of Practical Immunohistochemistry

View full text Add to dashboard Cite

Concordance in BRAF V600E status over time in malignant melanoma and corresponding metastases

Cited by 11 publications

References 36 publications

High concordance of BRAF mutational status in matched primary and metastatic melanoma

High concordance of BRAF mutational status in matched primary and metastatic melanoma

A Deep Learning Approach for Rapid Mutational Screening in Melanoma

Skin

Contact Info

Product

Resources

About