title: Chondroitin sulfate synthase 1 expression is associated with malignant potential of soft tissue sarcomas with myxoid substance.
abstract: The glycosyltransferases chondroitin sulfate synthase 1 (CHSY1) and exostoses-like 3 (EXTL3) specifically function in biosynthesis of the glycans chondroitin sulfate and heparan sulfate, respectively. Although these glycans play important roles in pathogenesis of various tumors, their significance in soft tissue sarcoma remains unknown. Here, we asked whether CHSY1 or EXTL3 expression correlates with malignant potential of soft tissue sarcomas with myxoid substance. To do so, we examined 40 samples representing specific types, including 12 cases of myxoid liposarcoma, 14 of myxofibrosarcoma, 12 of malignant peripheral nerve sheath tumor, and 2 of low-grade fibromyxoid sarcoma. We performed immunohistochemistry with anti-CHSY1 and anti-EXTL3 antibodies and compared enzyme expression levels with tumor histologic grade as assessed by the Fédération Nationale des Centres de Lutte Contre le Cancer classification and with patient 5-year survival rate. CHSY1 and EXTL3 were expressed in 72.5% and 32.5% of all tumors, respectively. Notably, CHSY1 was strongly expressed in myxofibrosarcoma and malignant peripheral nerve sheath tumor compared with other tumors and significantly associated with higher- rather than lower-grade tumors (P < .01). High expression of CHSY1 was also significantly associated with poorer patient outcomes (P = .031) and higher stages assessed by American Joint Committee on Cancer staging system (P = .004). By contrast, EXTL3 expression was not correlated with histologic grade or patient prognosis. We conclude that CHSY1 expression is closely associated with malignant potential of soft tissue sarcomas with myxoid substance.
authors.affiliation: Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan; Department of Orthopedics, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
authors.forename: Takashige
authors.initials: T
authors.lastname: Momose
authors.affiliation: Department of Orthopedics, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshimura
authors.affiliation: Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Harumiya
authors.affiliation: Department of Orthopedics, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
authors.forename: Ken'ichi
authors.initials: K
authors.lastname: Isobe
authors.affiliation: Department of Orthopedics, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
authors.forename: Munehisa
authors.initials: M
authors.lastname: Kito
authors.affiliation: Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan.
authors.forename: Mana
authors.initials: M
authors.lastname: Fukushima
authors.affiliation: Department of Orthopedics, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan. Electronic address: jnaka@shinshu-u.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Nakayama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002648:Child; D005260:Female; D005350:Fibroma / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005354:Fibrosarcoma / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D014453:Glucuronosyltransferase; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D018208:Liposarcoma, Myxoid / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D064251:Multifunctional Enzymes; D017350:N-Acetylgalactosaminyltransferases / Q000032:analysis* / Q000235:genetics; D017351:N-Acetylglucosaminyltransferases / Q000032:analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018317:Nerve Sheath Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016016:Proportional Hazards Models; D012983:Soft Tissue Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C110774:EXTL3 protein, human; D064251:Multifunctional Enzymes; D017350:N-Acetylgalactosaminyltransferases; D017351:N-Acetylglucosaminyltransferases; D014453:Glucuronosyltransferase; C498800:CHSY1 protein, human
keywords: CHSY1; Chondroitin sulfate; EXTL3; Heparan sulfate; Soft tissue sarcoma