Uterine Inflammatory Myofibroblastic Tumors Frequently Harbor ALK Fusions With IGFBP5 and THBS1
| Autor: | W. Glenn McCluggage, Eleanor Koay, Brian A. Kudlow, Jen-Chieh Lee, Tony Ng, Josh Haimes, Cheng-Han Lee, Colin J.R. Stewart, Bo Meng, Brady P. Culver, Ann Whitehouse, Nichola Cope |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
0301 basic medicine Pathology medicine.medical_specialty Granuloma Plasma Cell Pathology and Forensic Medicine Thrombospondin 1 Fusion gene 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases medicine ROS1 Humans Anaplastic lymphoma kinase Anaplastic Lymphoma Kinase Aged Gene Library Uterine sarcoma medicine.diagnostic_test Sequence Analysis RNA business.industry Receptor Protein-Tyrosine Kinases Middle Aged medicine.disease Immunohistochemistry Insulin-Like Growth Factor Binding Proteins 030104 developmental biology Myxoid Leiomyoma Fusion transcript 030220 oncology & carcinogenesis Uterine Neoplasms Smooth Muscle Tumor RNA Female Surgery Gene Fusion Anatomy business Fluorescence in situ hybridization |
| Zdroj: | American Journal of Surgical Pathology. 41:773-780 |
| ISSN: | 0147-5185 |
| DOI: | 10.1097/pas.0000000000000801 |
| Popis: | Inflammatory myofibroblastic tumor (IMT) can occur in a number of anatomic sites, including the uterus. Like its soft tissue counterpart, uterine IMT frequently expresses ALK and harbors ALK genetic rearrangements. The aim of this study is to fully characterize the genetic fusions that occur in uterine IMT. We studied 11 uterine IMTs with typical histology and 8 uterine myxoid smooth muscle tumors (5 leiomyomas, 1 smooth muscle tumor of uncertain malignant potential, and 2 leiomyosarcomas) in which the differential of IMT was considered, using a RNA-sequencing-based fusion assay to detect genetic fusions involving ALK, ROS1, RET, NTRK1/3, and other genes. ALK was expressed in 10 of 11 IMTs and 1 tumor initially categorized as a myxoid leiomyoma (granular cytoplasmic staining with paranuclear accentuation). Fusion transcripts involving ALK were identified in 9 of 10 ALK immunopositive IMTs, with 3 harboring IGFBP5-ALK, 3 harboring THBS1-ALK, 2 harboring FN1-ALK, and 1 harboring TIMP3-ALK. Among the smooth muscle tumors, IGFBP5-ALK fusion transcript was identified in only 1 ALK immunopositive case. Further review revealed that although a diagnosis of IMT was considered for the ALK immunopositive myxoid leiomyoma, this diagnosis was not initially rendered only because fluorescence in situ hybridization analysis was interpreted as negative for ALK genetic rearrangement; this case is best reclassified as an IMT. Notably, all the ALK fusions identified in our study included the transmembrane domain-encoding exon 19 of ALK. Our findings confirm the high frequency of ALK fusions in uterine IMT, with an enrichment of novel 5' ALK fusion partners (IGFBP5, THBS1, and TIMP3) and exon 19-containing ALK fusion. Given that IGFBP5 and FN1 are both situated on the same chromosome as ALK, fluorescence in situ hybridization analysis for ALK rearrangement may not be reliable and a negative result should not exclude a diagnosis of uterine IMT if the histologic features and ALK immunostaining findings are supportive. |
| Databáze: | OpenAIRE |
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