The value of ZAP-70 mRNA and CD38 protein expression as surrogate markers of IgVH mutation status in CLL. (A) Distribution of ZAP-70 mRNA expression levels as measured by DNA microarrays in CLL subtypes. The dashed line indicates the optimal cutoff for distinguishing Ig-unmutated and Ig-mutated CLL. (B) Distribution of CD38 protein expression as measured by flow cytometry and expressed as the percentage of CLL cells more intensely stained with CD38 than with an immunoglobulin isotype control. (C) ZAP-70 mRNA expression is a better predictor of IgVH mutation status than CD38 protein expression. (D) ZAP-70 as a surrogate marker of IgVH mutation status is associated with lower false-positive and false-negative rates than CD38.