Interpretation of Anti-ALK Immunohistochemistry Results

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Interpretation of Anti-ALK Immunohistochemistry Results Kengo Takeuchi, MD, PhD Journal of Thoracic Oncology Volume 8, Issue 7, Pages e67-e68 (July 2013) DOI: 10.1097/JTO.0b013e318293e1ff Copyright © 2013 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 ALK iAEP IHC in lung cancers with or without ALK fusion genes. Expression of ALK fusion protein is dependent on the promoter-enhancer activity of ALK partner genes, including EML4, which are usually housekeeping genes. In ALK fusion-positive tumors, therefore, all tumor cells are immunostained for the ALK kinase domain in IHC using anti-ALK antibody directed to the kinase domain, when stained appropriately by using a highly sensitive method, such as iAEP. All the cancer cells in an EML4–ALK-positive lung cancer express EML4-ALK protein (A). Some lung cancer cases (<1%) may express full length ALK. In such a case, the staining intensity usually varies from cell to cell, showing staining heterogeneity. This heterogeneity is probably because ALK expression in these cases is physiological, as in normal nerve cells, and because the ALK promoter-enhancer activity varies among cells. ALK rearrangement-negative small-cell carcinoma (B), large-cell neuroendocrine carcinoma (C), and poorly differentiated carcinoma (squamous cell carcinoma in this case, D) of lung may sometimes express the full length ALK, and the staining pattern is usually heterogeneous. IHC, immunohistochemistry; ALK, anaplastic lymphoma kinase; iAEP, intercalated antibody-enhanced polymer. Journal of Thoracic Oncology 2013 8, e67-e68DOI: (10.1097/JTO.0b013e318293e1ff) Copyright © 2013 International Association for the Study of Lung Cancer Terms and Conditions