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

Abstract

Aims

The present study analysed the usability of an immunohistochemical (IHC) analysis compared to a frequently used mutation detection analysis and examined the extent of intra- and inter-tumour heterogeneity of BRAF V600E in primary tumours and their corresponding metastases. In the development of inter-tumour heterogeneity between the primary tumour and the corresponding metastases, time as a factor was also investigated.

Methods

In total, 227 samples from 224 melanoma patients were analysed using both the Cobas^® 4800 BRAF V600 Mutation test and IHC anti-BRAF V600E staining. In 82 primary tumours and 224 corresponding metastases, the extent of inter- and intra-tumour heterogeneity was investigated using IHC staining.

Results

In 15 cases, disagreement between IHC analysis and the Cobas test was seen. In all but one of the examined patients, homogeneity between the primary tumour and the corresponding metastasis was found. Except for this one case, no heterogeneity developed over longer periods.

Conclusion

IHC analysis can be safely used as a BRAF pre-therapy screening tool, and no additional test is needed when staining is positive. However, if stains are negative, additional tests are essential for detection of other BRAF mutations. We suggest that using primary melanoma tissues is just as safe as using metastatic tissue for detection of BRAF V600E, since BRAF inter-tumour heterogeneity is extremely rare. In addition, the time between diagnosis of the primary tumour and diagnosis of the corresponding metastasis seems not to increase the risk of inter-tumour heterogeneity

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