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Uterine Inflammatory Myofibroblastic Tumors Frequently Harbor ALK Fusions With IGFBP5 and THBS1.

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dc.creator Haimes, J. D.
dc.creator Stewart, C. J. R.
dc.creator Kudlow, B. A.
dc.creator Culver, B. P.
dc.creator Meng, B.
dc.creator Koay, E.
dc.creator Whitehouse, A.
dc.creator Cope, Nichola
dc.creator Lee, J-C
dc.creator Ng, T.
dc.creator McCluggage, W. G.
dc.creator Lee, C-H
dc.date 2017-07-20T14:05:30Z
dc.date 2017-07-20T14:05:30Z
dc.date 2017-06
dc.date.accessioned 2023-02-17T19:47:36Z
dc.date.available 2023-02-17T19:47:36Z
dc.identifier Uterine Inflammatory Myofibroblastic Tumors Frequently Harbor ALK Fusions With IGFBP5 and THBS1. 2017, 41 (6):773-780 Am. J. Surg. Pathol.
dc.identifier 1532-0979
dc.identifier 28490045
dc.identifier 10.1097/PAS.0000000000000801
dc.identifier http://hdl.handle.net/11287/620372
dc.identifier The American journal of surgical pathology
dc.identifier.uri http://localhost:8080/xmlui/handle/CUHPOERS/241976
dc.description 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.
dc.language en
dc.publisher Wolters Kluwer
dc.relation http://insights.ovid.com/pubmed?pmid=28490045
dc.rights Archived with thanks to The American journal of surgical pathology
dc.subject Wessex Classification Subject Headings::Clinical pathology
dc.title Uterine Inflammatory Myofibroblastic Tumors Frequently Harbor ALK Fusions With IGFBP5 and THBS1.
dc.type Journal Article
dc.type Published


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