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Immunohistochemistry As an Accurate Tool for the Assessment of and Mutations in Primary and Metastatic Melanoma

Abstract

Metastatic melanoma is a fatal disease with poor prognosis. Ever since targeted therapy against oncogenic was approved, molecular profiling has become an integral part of the management of such patients. While molecular testing is not available in all pathology laboratories, immunohistochemistry (IHC) is a reliable screening option. The major objective of the present study was to evaluate whether IHC detection of and the tumor (suppressor) protein 53 gene () are reliable surrogates for mutation detection. Formalin-fixed paraffin-embedded samples of melanomas for which molecular data were previously obtained by targeted next-generation sequencing (NGS) between January 2014 and February 2019 were immunostained with BRAF V600E and p53 antibodies. A blinded evaluation of the IHC slides was performed by two pathologists in order to evaluate inter-observer concordance (discordant cases were reviewed by a third observer). The associations between the results of IHC and molecular profiling were evaluated. The study included a series of 37 cases of which 15 harbored a mutation and five a mutation. IHC had an overall diagnostic accuracy of 93.9% for and 68.8% for compared to NGS. A statistically significant association between the two diagnostic methods was obtained for BRAF V600E (P=0.0004) but not for p53 (P=0.3098) IHC. The κ coefficient for IHC assessment of p53 was 0.55 and that for BRAF V600E was 0.72. In conclusion, the present results evidenced that IHC staining is a reliable surrogate for NGS in identifying the mutation, which may become an efficient screening tool. Aberrant expression of p53 on IHC is at times associated with mutations but it was not possible to establish a direct link.

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