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Expression of ROS1 predicts ROS1 gene rearrangement in inflammatory myofibroblastic tumors.
Mod Pathol 2015; 28(5):732-9MP

Abstract

Inflammatory myofibroblastic tumor is a distinctive, rarely metastasizing mesenchymal neoplasm composed of fascicles of spindle cells with a prominent inflammatory infiltrate. Roughly 50% of inflammatory myofibroblastic tumors harbor ALK receptor tyrosine kinase gene rearrangements. Such tumors are usually positive for ALK by immunohistochemistry. The molecular pathogenesis of ALK-negative inflammatory myofibroblastic tumors is largely unknown. A recent study identified rearrangements of ROS1 (another tyrosine kinase receptor) in a subset of ALK-negative inflammatory myofibroblastic tumors. Immunohistochemistry for ROS1 has been shown to correlate with ROS1 rearrangement in lung adenocarcinomas. The purpose of this study was to determine whether immunohistochemistry for ROS1 could predict ROS1 rearrangement in inflammatory myofibroblastic tumor. In total, 30 inflammatory myofibroblastic tumors were evaluated, including 21 ALK-positive tumors (10 confirmed to harbor ALK rearrangements, with TPM3, CLTC, RANPB2, and FN1 fusion partners) and 9 ALK-negative tumors (including 2 known to harbor ROS1 rearrangements). Immunohistochemistry was performed on whole tissue sections following pressure cooker antigen retrieval using a rabbit anti-ROS1 monoclonal antibody. The results were scored as 'positive' or 'negative,' and the pattern of staining was recorded. Three ALK-negative inflammatory myofibroblastic tumors (including both tumors with known ROS1 rearrangements) showed immunoreactivity for ROS1, whereas all ALK-positive inflammatory myofibroblastic tumors were negative for ROS1. One ROS1-positive inflammatory myofibroblastic tumor (with YWHAE-ROS1 fusion) showed strong, diffuse cytoplasmic and nuclear staining; one case (with TFG-ROS1 fusion) showed weak, diffuse and dot-like cytoplasmic staining; and one case (fusion partner unknown) showed moderate, diffuse and dot-like cytoplasmic staining. Expression of ROS1 correlates with ROS1 gene rearrangement in inflammatory myofibroblastic tumor. These findings suggest that immunohistochemistry for ROS1 may be useful to support the diagnosis of a subset of inflammatory myofibroblastic tumors and may select some clinically aggressive cases for targeted therapy directed against ROS1.

Authors+Show Affiliations

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.1] Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA [2] Department of Medicine, Vanderbilt University School of Medicine and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25612511

Citation

Hornick, Jason L., et al. "Expression of ROS1 Predicts ROS1 Gene Rearrangement in Inflammatory Myofibroblastic Tumors." Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, vol. 28, no. 5, 2015, pp. 732-9.
Hornick JL, Sholl LM, Dal Cin P, et al. Expression of ROS1 predicts ROS1 gene rearrangement in inflammatory myofibroblastic tumors. Mod Pathol. 2015;28(5):732-9.
Hornick, J. L., Sholl, L. M., Dal Cin, P., Childress, M. A., & Lovly, C. M. (2015). Expression of ROS1 predicts ROS1 gene rearrangement in inflammatory myofibroblastic tumors. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 28(5), pp. 732-9. doi:10.1038/modpathol.2014.165.
Hornick JL, et al. Expression of ROS1 Predicts ROS1 Gene Rearrangement in Inflammatory Myofibroblastic Tumors. Mod Pathol. 2015;28(5):732-9. PubMed PMID: 25612511.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of ROS1 predicts ROS1 gene rearrangement in inflammatory myofibroblastic tumors. AU - Hornick,Jason L, AU - Sholl,Lynette M, AU - Dal Cin,Paola, AU - Childress,Merrida A, AU - Lovly,Christine M, Y1 - 2015/01/23/ PY - 2014/08/21/received PY - 2014/12/03/revised PY - 2014/12/15/accepted PY - 2015/1/24/entrez PY - 2015/1/24/pubmed PY - 2016/2/26/medline SP - 732 EP - 9 JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JO - Mod. Pathol. VL - 28 IS - 5 N2 - Inflammatory myofibroblastic tumor is a distinctive, rarely metastasizing mesenchymal neoplasm composed of fascicles of spindle cells with a prominent inflammatory infiltrate. Roughly 50% of inflammatory myofibroblastic tumors harbor ALK receptor tyrosine kinase gene rearrangements. Such tumors are usually positive for ALK by immunohistochemistry. The molecular pathogenesis of ALK-negative inflammatory myofibroblastic tumors is largely unknown. A recent study identified rearrangements of ROS1 (another tyrosine kinase receptor) in a subset of ALK-negative inflammatory myofibroblastic tumors. Immunohistochemistry for ROS1 has been shown to correlate with ROS1 rearrangement in lung adenocarcinomas. The purpose of this study was to determine whether immunohistochemistry for ROS1 could predict ROS1 rearrangement in inflammatory myofibroblastic tumor. In total, 30 inflammatory myofibroblastic tumors were evaluated, including 21 ALK-positive tumors (10 confirmed to harbor ALK rearrangements, with TPM3, CLTC, RANPB2, and FN1 fusion partners) and 9 ALK-negative tumors (including 2 known to harbor ROS1 rearrangements). Immunohistochemistry was performed on whole tissue sections following pressure cooker antigen retrieval using a rabbit anti-ROS1 monoclonal antibody. The results were scored as 'positive' or 'negative,' and the pattern of staining was recorded. Three ALK-negative inflammatory myofibroblastic tumors (including both tumors with known ROS1 rearrangements) showed immunoreactivity for ROS1, whereas all ALK-positive inflammatory myofibroblastic tumors were negative for ROS1. One ROS1-positive inflammatory myofibroblastic tumor (with YWHAE-ROS1 fusion) showed strong, diffuse cytoplasmic and nuclear staining; one case (with TFG-ROS1 fusion) showed weak, diffuse and dot-like cytoplasmic staining; and one case (fusion partner unknown) showed moderate, diffuse and dot-like cytoplasmic staining. Expression of ROS1 correlates with ROS1 gene rearrangement in inflammatory myofibroblastic tumor. These findings suggest that immunohistochemistry for ROS1 may be useful to support the diagnosis of a subset of inflammatory myofibroblastic tumors and may select some clinically aggressive cases for targeted therapy directed against ROS1. SN - 1530-0285 UR - https://www.unboundmedicine.com/medline/citation/25612511/Expression_of_ROS1_predicts_ROS1_gene_rearrangement_in_inflammatory_myofibroblastic_tumors_ L2 - http://dx.doi.org/10.1038/modpathol.2014.165 DB - PRIME DP - Unbound Medicine ER -