M. A. Anwar1, F. Murad1, E. Dawson1, Z. Y. Abd Elmageed1, K. Tsumagari1, E. Kandil1 1Tulane University School Of Medicine,General Surgery,New Orleans, LA, USA
Introduction:
BRAF-V600E mutation is associated with tumor aggressiveness and poor prognosis in melanoma patients. Identification of this mutation is clinically important as we now have FDA-approved targeted therapies, such as BRAF and MEK inhibitors, which have shown to retard the disease progression in these patients. Detection of BRAF-V600E by genetic analysis using PCR is the gold standard method for melanoma cases. However, immunohistochemistry (IHC) using VE1 antibody is rapidly immerging as a trustworthy method for determination of mutation status in patients’ specimens.
Objective:
To assess the reliability of IHC compared to genetic methods for successful identification of BRAF-V600E mutation in melanoma tissue specimens.
Study
Design:
Systematic review and meta-analysis of English language studies comparing IHC with genetic analysis for the detection of BRAF-V600E mutation in melanoma patients was performed.
Methods:
A literature search of PubMed, Web of Science, and Embase was performed for studies comparing IHC to genetic analysis for the detection of BRAF in melanoma patients published through May 28, 2015. Pooled sensitivity, specificity, diagnostic odds ratio, positive and negative likelihood ratios were calculated using a bivariate model. Logit estimates of sensitivity and specificity with their respective variances were used to plot a hierarchical ROC curve and area under the curve. Heterogeneity was assessed using the Q and I-squared statistics.
Results:
Initial literature search resulted in 287 articles. After two independent reviews and consensus-based discussion to resolve disparities; 21 studies involving a total of 1,753 cases met the eligibility criteria and were included in the analysis. The pooled sensitivity of IHC was 0.97; 95% CI (0.94-0.98), specificity 0.99; 95% CI (0.97-1.00), positive likelihood ratio 158.3; 95% CI (33.8-740.8), negative likelihood ratio 0.03; 95% CI (0.02-0.06), and diagnostic odds ratio 4672 (1104-19780). A high heterogeneity was observed between these studies (Q value of 28.77 & I2 value of 93; 95% CI (87-99) which may be explained by studies using different cutoff values for interpretation of IHC. High accuracy of IHC was depicted by AUC in the ROC curve which was 0.99; 95 % CI (0.98-1.00).
Conclusion:
Meta-analysis demonstrates that IHC is highly sensitive and specific for the detection of BRAF-V600E in melanoma cases. IHC is likely to be useful method in BRAF mutation detection because it is highly comparable to the genetic methods. Any negative or low staining cases may be selected to undergo genetic analysis based on other clinical and histopathological features.
