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

2.50
Hdl Handle:
http://hdl.handle.net/11287/620372
Title:
Uterine Inflammatory Myofibroblastic Tumors Frequently Harbor ALK Fusions With IGFBP5 and THBS1.
Authors:
Haimes, J. D.; Stewart, C. J. R.; Kudlow, B. A.; Culver, B. P.; Meng, B.; Koay, E.; Whitehouse, A.; Cope, Nichola; Lee, J-C; Ng, T.; McCluggage, W. G.; Lee, C-H
Abstract:
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.
Citation:
Uterine Inflammatory Myofibroblastic Tumors Frequently Harbor ALK Fusions With IGFBP5 and THBS1. 2017, 41 (6):773-780 Am. J. Surg. Pathol.
Publisher:
Wolters Kluwer
Journal:
The American journal of surgical pathology
Issue Date:
Jun-2017
URI:
http://hdl.handle.net/11287/620372
DOI:
10.1097/PAS.0000000000000801
PubMed ID:
28490045
Additional Links:
http://insights.ovid.com/pubmed?pmid=28490045
Type:
Journal Article
Language:
en
ISSN:
1532-0979
Appears in Collections:
Exeter Clinical Laboratory International (Blood Sciences, Genetics, Cellular Pathology & Microbiology); 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorHaimes, J. D.en
dc.contributor.authorStewart, C. J. R.en
dc.contributor.authorKudlow, B. A.en
dc.contributor.authorCulver, B. P.en
dc.contributor.authorMeng, B.en
dc.contributor.authorKoay, E.en
dc.contributor.authorWhitehouse, A.en
dc.contributor.authorCope, Nicholaen
dc.contributor.authorLee, J-Cen
dc.contributor.authorNg, T.en
dc.contributor.authorMcCluggage, W. G.en
dc.contributor.authorLee, C-Hen
dc.date.accessioned2017-07-20T14:05:30Z-
dc.date.available2017-07-20T14:05:30Z-
dc.date.issued2017-06-
dc.identifier.citationUterine Inflammatory Myofibroblastic Tumors Frequently Harbor ALK Fusions With IGFBP5 and THBS1. 2017, 41 (6):773-780 Am. J. Surg. Pathol.en
dc.identifier.issn1532-0979-
dc.identifier.pmid28490045-
dc.identifier.doi10.1097/PAS.0000000000000801-
dc.identifier.urihttp://hdl.handle.net/11287/620372-
dc.description.abstractInflammatory 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.en
dc.language.isoenen
dc.publisherWolters Kluweren
dc.relation.urlhttp://insights.ovid.com/pubmed?pmid=28490045en
dc.rightsArchived with thanks to The American journal of surgical pathologyen
dc.subjectWessex Classification Subject Headings::Clinical pathologyen
dc.titleUterine Inflammatory Myofibroblastic Tumors Frequently Harbor ALK Fusions With IGFBP5 and THBS1.en
dc.typeJournal Articleen
dc.identifier.journalThe American journal of surgical pathologyen
dc.type.versionPublisheden

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