ALK and ROS1 Overexpression is Very Rare in Colorectal Adenocarcinoma. Issue 2 (February 2015)

• Record Type: Journal Article
• Authors: Houang, Michelle; Toon, Christopher W.; Clarkson, Adele; Sioson, Loretta; de Silva, Keshani; Watson, Nicole; Singh, Nisha R.; Chou, Angela; Gill, Anthony J.
• Is Part Of: Applied immunohistochemistry & molecular morphology. Volume 23:Issue 2(2015)
• Publication Date: 2015-02
• Subjects: Diagnostic immunohistochemistry -- Periodicals; Immunohistochemistry -- Periodicals; Cells -- Morphology -- Periodicals; Molecular diagnosis -- Periodicals; 616.079
• DOI: 10.1097/PAI.0000000000000025
• Languages: English
• ISSNs: 1541-2016

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>Crizotinib, a small molecule tyrosine kinase inhibitor, has shown tremendous promise in the treatment of lung adenocarcinomas harboring either <italic>ALK</italic> or <italic>ROS1</italic> rearrangements. Recently, small studies of colorectal carcinomas (CRCs) have suggested an incidence of <italic>EML4-ALK</italic> translocations of 0.4% to 2.4% and <italic>FIG-ROS1</italic> translocations of 0.8%. In lung cancer, screening immunohistochemical staining for ALK and ROS1 has been validated as highly sensitive for these translocations, but this has not been investigated in CRC. We therefore sought to investigate the incidence of ALK and ROS1 overexpression as detected by immunohistochemical staining in a large cohort of CRCs. Of the 1889 CRCs, only 1 case (0.05%) demonstrated diffuse strong positive staining for ALK, whereas 14 (0.7%) showed weak nonspecific staining; the remainder were negative. The 1 positive case was confirmed to harbor an <italic>ALK</italic> rearrangement by fluorescent in situ hybridization (FISH), whereas the 14 tumors with weak staining were FISH-negative. The ALK positive case demonstrated positive expression in all dysplastic and malignant cells indicating that the translocation was an early clonal event. No cases were positive for ROS1 by immunohistochemical staining, although 2 cases did show some nonspecific staining and were shown to be negative for <italic>ROS1</italic> translocation by FISH. We conclude that although diffuse strong positive staining for ALK is likely to be highly specific for <italic>ALK</italic> rearrangement in CRC, both ALK and ROS1 immunohistochemical staining are very low-yield tests and difficult to justify in the routine clinical setting.</p> </sec> </abstract>