title: Extraskeletal myxoid chondrosarcoma of the vulva with PLAG1 gene activation: molecular genetic characterization of 2 cases.
abstract: Extraskeletal myxoid chondrosarcoma (EMC) is a rare mesenchymal neoplasm, rarely reported in the genitourinary tract with only 5 cases reported in the vulva. We investigated 2 cases of vulvar sarcomas whose morphologic appearance and immunohistochemical profiles were consistent with EMC using fluorescence in situ hybridization (FISH), reverse-transcription polymerase chain reaction, and a whole genome expression array. FISH and reverse-transcription polymerase chain reaction assays showed no EWSR1 and NR4A3 loci rearrangements. Microarray-based analysis also revealed no changes in NR4A3 and EWSR1 gene transcription levels. Microarray data showed a significant downregulation of the muscle-related genes (eg, myosin heavy chain family, actins, myoglobin, desmin, creatine kinase, troponins) and cytokeratins (KRT6A, 6B, 13, 14, and 78), upregulation of several neuron-specific genes [neural cell adhesion molecule 1 (NCAM-1/CD56), neurofilament (NEFH)], along with some well-characterized tumor biomarkers [carbonic anhydrase IX (CA-9), topoisomerase IIα (TOP2A), matrix metalloproteinases (MMP-7, MMP-9), CDKN2 gene (p16-INK4a), checkpoint homolog 2 (CHEK2)]. Notably, both tumors showed upregulation of the pleomorphic adenoma gene 1 (PLAG1), and in 1 case PLAG1 gene rearrangement was detected by break-apart FISH. Some vulvar tumors with morphologic and immunohistochemical characteristics of EMC may represent a molecular genetic entity separate from EMCs arising in other locations. PLAG1 gene activation appears to be involved in the development of these neoplasms.
authors.affiliation: *Department of Pathology and Cytology ∥Department of Obstetrics and Gynecology, University Hospital Center Zagreb §Department of Pathology, University of Zagreb Medical School, Zagreb, Croatia †Caris Life Sciences, Phoenix, AZ ‡Robert Jones and Agnes Hunt Orthopaedic and District Hospital, Oswestry and Royal Orthopaedic Hospital, Birmingham, UK ¶Department of Pathology, Clinical Center of the University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
authors.forename: Snjezana
authors.initials: S
authors.lastname: Dotlic
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gatalica
authors.forename: Wenhsiang
authors.initials: W
authors.lastname: Wen
authors.forename: Anatole
authors.initials: A
authors.lastname: Ghazalpour
authors.forename: Chas
authors.initials: C
authors.lastname: Mangham
authors.forename: Damir
authors.initials: D
authors.lastname: Babic
authors.forename: Josko
authors.initials: J
authors.lastname: Zekan
authors.forename: Semir
authors.initials: S
authors.lastname: Vranic
mesh_terms: D002813:Chondrosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D018204:Neoplasms, Connective and Soft Tissue / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014846:Vulvar Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C104382:PLAG1 protein, human