Immunohistochemistry (IHC) is a widely-tested, low-cost and rapid ancillary technique
available in all laboratories of pathology. This method is generally used for diagnostic purposes, but
several studies have investigated the sensitivity and specificity of different immunohistochemical antibodies
as a surrogate test in the determination of predictive biomarkers in non-small cell lung cancer
(NSCLC), particularly for Epidermal Growth Factor Receptor (EGFR) gene mutations, Anaplastic
Lymphoma Kinase (ALK) gene and ROS1 rearrangements. In this review, a critical examination of the
works comparing the consistency of IHC expression and conventional molecular techniques to identify
genetic alterations with predictive value in NSCLC is discussed. Summarizing, data on sensitivity and
specificity of antibodies against ALK and ROS1 are very consistent and time has come to trust in IHC
at least as a cost-effective screening tool to identify patients with rearranged tumors in clinical practice.
On the other hand, mutant-specific antibodies against EGFR demonstrate a good specificity but a lowto-
fair sensitivity, raising some cautions on their employment as robust predictive biomarkers. A brief
comment on preliminary experiences with antibodies against BRAF, RET, HER2 and c-MET is also included.
Keywords: ALK, EGFR, gene mutation, immunohistochemistry, lung cancer, molecular biology, ROS1.
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