A literature search of PubMed, Web of Science, and Embase was performed for studies comparing IHC with 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 receiver operating characteristic curve and area under the curve. Heterogeneity was assessed using the Q- and I-squared statistics.
An initial literature search resulted in 287 articles. After two independent reviews and consensus-based discussion to resolve disparities, 21 studies involving a total of 1687 cases met the eligibility criteria and were included in the analysis. The pooled sensitivity of IHC for BRAF-V600E detection was 0.96; 95% confidence interval (CI, 0.94-0.98), specificity 1.00; 95% CI (0.97-1.00), positive likelihood ratio 194.2; 95% CI (37.6-1003.3), negative likelihood ratio 0.04; 95% CI (0.02-0.07), and diagnostic odds ratio 5503 (1199-25,263), as compared with genetic analysis. A high heterogeneity was observed between these studies (Q value of 40.17 & I2 = 95%; 95% CI (91-99, P < 0.001) which may be explained by studies using different cutoff values for labeling IHC as positive. High accuracy of IHC was depicted by area under the curve in the receiver operating characteristic curve which was 0.99; 95 % CI (0.98-1.00).
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 in BRAF mutation detection because it is highly comparable with the genetic methods. Any negative or low staining cases may be selected to undergo genetic analysis based on other clinical and histopathologic features.