title: Congenital mesoblastic nephroma: a study of 19 cases using immunohistochemistry and ETV6-NTRK3 fusion gene rearrangement.
abstract: Mesoblastic nephroma (MN) is the most common renal tumour in the first 3 months of life and accounts for 3-5% of all paediatric renal neoplasms. To further understand the morphological variants of MN, we identified 19 cases of MN (five classic, eight cellular and six mixed) and examined each case for markers known to be important in urogenital embryological development (PAX8, WT1 and RCC), stem cell associated markers (Oct 4, CD34 and c-kit), muscle/myofibroblastic markers (muscle specific actin, calponin and h-caldesmon), aberrant transcription factors, cell cycle regulation and other oncogenic proteins (p16, cyclin D1 and beta-catenin). Fluorescence in situ hybridisation (FISH) testing for ETV6-NTRK3 gene fusion/rearrangement revealed further differentiation between the subtypes with ETV6-NTRK3 gene fusion detected in 0/5 of the classic MN, 8/8 of the cellular MN and 5/6 of the mixed MN cohorts, respectively. Our results conclude that cyclin D1 and beta-catenin may be useful markers for differentiating between cellular MN and classic MN when the histology is not conclusive. The absence of expression of stem cell markers and markers involved in urogenital development suggests that MN is not a nephroma and most likely represents a soft tissue tumour, with congenital infantile fibrosarcoma representing cellular MN with a predilection to arise in the kidney. In addition, the immunophenotype and genetic fingerprint of mixed MN most likely represents a heterogenous group of tumours that are mostly cellular type, with areas that are phenotypically less cellular.
authors.affiliation: Children's Hospital of Eastern Ontario and University of Ottawa, Canada. Electronic address: deldemellawy@cheo.on.ca.
authors.forename: Dina
authors.initials: D
authors.lastname: El Demellawy
authors.affiliation: Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, United States.
authors.forename: Caitlin A
authors.initials: CA
authors.lastname: Cundiff
authors.affiliation: Children's Hospital of Eastern Ontario and University of Ottawa, Canada.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Nasr
authors.affiliation: Children's Hospital of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, United States.
authors.forename: John A
authors.initials: JA
authors.lastname: Ozolek
authors.affiliation: Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, United States.
authors.forename: Nancy
authors.initials: N
authors.lastname: Elawabdeh
authors.affiliation: Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, United States.
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Caltharp
authors.affiliation: Children's Hospital of Eastern Ontario and University of Ottawa, Canada.
authors.forename: Pourya
authors.initials: P
authors.lastname: Masoudian
authors.affiliation: Children's Hospital of Eastern Ontario and University of Ottawa, Canada.
authors.forename: Katrina J
authors.initials: KJ
authors.lastname: Sullivan
authors.affiliation: Children's Hospital of Eastern Ontario and University of Ottawa, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: de Nanassy
authors.affiliation: Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, United States.
authors.forename: Bahig M
authors.initials: BM
authors.lastname: Shehata
mesh_terms: D019938:Cyclin D1 / Q000378:metabolism*; D005260:Female; D005354:Fibrosarcoma / Q000151:congenital / Q000235:genetics / Q000473:pathology*; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007680:Kidney Neoplasms / Q000151:congenital / Q000235:genetics / Q000473:pathology*; D008297:Male; D018201:Nephroma, Mesoblastic / Q000151:congenital / Q000235:genetics / Q000473:pathology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D012983:Soft Tissue Neoplasms / Q000151:congenital / Q000235:genetics / Q000473:pathology*; D051176:beta Catenin / Q000378:metabolism*; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D019938:Cyclin D1; D015514:Oncogene Proteins, Fusion; D051176:beta Catenin; C530104:CCND1 protein, human; C484319:ETV6-NTRK3 fusion protein, human; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein
keywords: Mesoblastic nephroma; cyclin D1; fusion gene