title: Pathology of soft-tissue tumors: daily diagnosis, molecular cytogenetics and experimental approach.
abstract: This article reviews problems in diagnostic pathology and molecular cytogenetics of soft-tissue tumors. Also discussed are the origin of soft-tissue sarcomas and the molecular basis of effective target therapy for sarcomas. Molecular cytogenetic analysis of tumor-specific chromosomal translocations and associated fusion gene transcripts offers a useful adjunct to the diagnosis of soft-tissue tumors, but recent studies have indicated a growing number of fusion gene variations in each tumor type. In pleomorphic sarcoma/malignant fibrous histiocytoma, the alternative lengthening of telomeres (ALT) mechanism may result in formation of anaphase bridges and marked nuclear pleomorphism. The histogenesis of soft-tissue sarcomas has been a matter of controversy. In the present experimental model using s.c. injection of 3-methylcholanthrene in C57BL/6 mice pretreated with bone marrow-transplantation from green fluorescent protein (GFP)-positive green mice, the bone marrow-derived mesenchymal stem cells as well as the tissue-resident mesenchymal cells in the peripheral soft tissues are possible originators of sarcomagenesis. Little is known about a molecular basis of target therapy for sarcomas. Platelet-derived growth factor-BB (PDGF-BB) enhances the invasive activity of malignant peripheral nerve sheath tumor (MPNST) cells through platelet-derived growth factor receptor (PDGFR) phosphorylation, whereas imatinib mesylate inhibited such activity, suggesting that targeting PDGFR-beta may result in the establishment of novel treatment for MPNST. In addition, emmprin is a transmembrane glycoprotein on tumor cells that stimulates peritumoral fibroblasts to produce matrix metalloproteinases (MMP), playing a crucial role in tumor progression, invasion and metastasis. The MMP upregulation mechanism mediated by tumor-associated emmprin may be a potentially useful target in anti-tumor invasion therapy for sarcomas.
authors.affiliation: Departments of Pathology, Fukuoka University Faculty of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, Japan. iwasaki@fukuokau.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nabeshima
authors.forename: Jun
authors.initials: J
authors.lastname: Nishio
authors.forename: Shiro
authors.initials: S
authors.lastname: Jimi
authors.forename: Mikiko
authors.initials: M
authors.lastname: Aoki
authors.forename: Kaori
authors.initials: K
authors.lastname: Koga
authors.forename: Makoto
authors.initials: M
authors.lastname: Hamasaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Ai
authors.initials: A
authors.lastname: Mogi
mesh_terms: D000818:Animals; D006801:Humans; D012983:Soft Tissue Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy