title: Cytoplasmic expression of Wilms tumor transcription factor-1 (WT1): a useful immunomarker for young-type fibromatoses and infantile fibrosarcoma.
abstract: There is increasing evidence that Wilms' tumor transcription factor-1 (WT1) is expressed in the cytoplasm of neoplastic cells from different benign and malignant tumors. Only a few studies on WT1 cytoplasmic immunolocalization are available in pediatric tumors. The aim of the present study was to investigate immunohistochemically the expression and distribution of WT1 in a large series of soft tissue fibroblastic/myofibroblastic lesions occurring in children and adolescents. Notably WT1 was not expressed in nodular fasciitis and desmoid-type (adult) fibromatosis, while it stained diffusely and strongly in several infantile-type fibromatoses, such as fibrous hamartoma of infancy, myofibroma/myofibromatosis, and lipofibromatosis. Interestingly, WT1 cytoplasmic expression was also found in all cases (10/10) of infantile fibrosarcomas examined. The present study shows that a diffuse WT1 cytoplasmic expression is of complementary diagnostic value to conventional myofibroblastic markers (α-smooth muscle actin; desmin) in confirming diagnosis of young-type fibromatoses or infantile fibrosarcoma and in ruling out both desmoid-type fibromatoses and nodular fasciitis. WT1 cytoplasmic expression in infantile fibrosarcoma is a novel finding which could be exploitable as an immunomarker for this tumor. Although highly sensitive, WT1 cytoplasmic immunostaining is not specific for infantile fibrosarcoma, and thus it should be evaluated in the context of a wide immunohistochemical panel when pathologists are dealing with spindle cell lesions of soft tissues in children and adolescents. Accordingly we recommend that a correct diagnosis of fibroblastic/myofibroblastic soft tissue lesion in pediatric patients is usually achieved on the basis of a careful correlation of morphological and immunohistochemical findings in the appropriate clinical context. The different cellular localization of WT1, namely nuclear, cytoplasmic or nucleo-cytoplasmic, in different benign and malignant tumors supports the hypothesis that this transcription factor plays a complex role in tumorigenesis, likely as a chameleon protein functioning as either a tumor suppressor gene or an oncogene, depending on cellular context.
authors.affiliation: Department G.F. Ingrassia, Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele" Anatomic Pathology, University of Catania, Catania, Italy. Electronic address: g.magro@unict.it.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Magro
authors.affiliation: Department G.F. Ingrassia, Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele" Anatomic Pathology, University of Catania, Catania, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Salvatorelli
authors.affiliation: Department G.F. Ingrassia, Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele" Anatomic Pathology, University of Catania, Catania, Italy.
authors.forename: Giada Maria
authors.initials: GM
authors.lastname: Vecchio
authors.affiliation: Department of Bio-Medical Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Musumeci
authors.affiliation: Department of Pathology, University of Padova, Padova, Italy.
authors.forename: Alaggio
authors.initials: A
authors.lastname: Rita
authors.affiliation: Department of Bio-Medical Sciences, Physiology Section, University of Catania, Catania, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Parenti
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005350:Fibroma / Q000378:metabolism* / Q000473:pathology; D005354:Fibrosarcoma / Q000378:metabolism* / Q000473:pathology; D006222:Hamartoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D021381:Protein Transport; D025721:WT1 Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D025721:WT1 Proteins; C583751:WT1 protein, human
keywords: Cytoplasmic expression; Fibromatoses; Immunohistochemistry; Infantile fibrosarcoma; WT1