title: Differential NF1, p16, and EGFR patterns by interphase cytogenetics (FISH) in malignant peripheral nerve sheath tumor (MPNST) and morphologically similar spindle cell neoplasms.
abstract: Malignant peripheral nerve sheath tumors (MPNSTs) are diagnostically challenging neoplasms for which sensitive and specific immunohistochemical markers are lacking. Although limited to date, previous studies have suggested that NF1 (17q), NF2 (22q), p16 (9p), and EGFR (7p) alterations may be involved in MPNST tumorigenesis. To determine whether specific genetic changes differentiate between MPNST and morphologically similar neoplasms, we assessed these chromosomal regions in 22 MPNSTs (9 NF1-associated, 13 sporadic), 13 plexiform neurofibromas, 5 cellular schwannomas, 8 synovial sarcomas, 6 fibrosarcomas, and 13 hemangiopericytomas by 2-color FISH. NF1 deletions, often in the form of monosomy 17, were found in MPNSTs (76%). neurofibromas (31%), hemangiopericytomas (17%), and fibrosarcomas (17%), but not in synovial sarcomas or cellular schwannomas. NF1 losses were encountered more frequently in MPNSTs versus other sarcomas (p < 0.001), as were p16 homozygous deletions (45% vs 0%; p < 0.001), EGFR amplifications (26% vs 0%; p = 0.006), and polysomies for either chromosomes 7 (53% vs 12%; p = 0.003) or 22 (50% vs 4%; p < 0.001). Hemizygous or homozygous p16 deletions were detected in 75% of MPNSTs, but not in benign nerve sheath tumors (p < 0.001). Thus, FISH analysis identifies relatively specific genetic patterns that may be useful in selected cases, for which the differential diagnosis includes low- or high-grade MPNST.
authors.affiliation: Department of Pathology, Washington University School of Medicine, St Louis, Missouri 63110-1093, USA.
authors.forename: Arie
authors.initials: A
authors.lastname: Perry
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Kunz
authors.forename: Christine E
authors.initials: CE
authors.lastname: Fuller
authors.forename: Ruma
authors.initials: R
authors.lastname: Banerjee
authors.forename: Edith F
authors.initials: EF
authors.lastname: Marley
authors.forename: Helen
authors.initials: H
authors.lastname: Liapis
authors.forename: Mark A
authors.initials: MA
authors.lastname: Watson
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
mesh_terms: D020732:Cytogenetic Analysis; D005784:Gene Amplification; D017353:Gene Deletion; D016514:Genes, Neurofibromatosis 1; D018773:Genes, erbB-1; D019942:Genes, p16; D006720:Homozygote; D006801:Humans; D007399:Interphase / Q000235:genetics*; D018317:Nerve Sheath Neoplasms / Q000235:genetics* / Q000473:pathology; D011132:Polyribosomes / Q000235:genetics