Title: High Concordance of BRAF Mutational Status in Matched Primary and Metastatic Melanoma Short Running Title: High Concordance of BRAF in Melanoma List of Authors:

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 tumours. There is uncertainty regarding the frequency with which BRAF status differs between primary and metastatic sites. This article is protected by copyright. All rights reserved. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/cup.13393 Methods: Between 2011 and 2016, 219 melanoma cases underwent BRAF testing in our institution. In 53 of these, paired primary and metastatic specimens were available for PCR and immunohistochemical evaluation. Results: 52 out of 53 cases (98%) showed concordant BRAF status between primary and metastatic site by 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, immunohistochemistry provided strong evidence that initial PCR testing had provided a false negative result due to low tumour volume. Thus, in cases where tissue is is difficult to obtain from a metastasis or unavailble, the primary tumour can be used with confidence.