title: Hyaluronan expression as a significant prognostic factor in patients with malignant peripheral nerve sheath tumors.
abstract: Hyaluronan (HA) regulates malignant tumor growth, invasion, and metastasis. However, few studies have focused on the roles of HA in tumorigenicity in malignant peripheral nerve sheath tumors (MPNST). In this study, we sought to clarify the prognostic value of HA in patients with MPNST. Specimens obtained from 15 patients with neurofibroma and 30 with MPNST were subjected to HA staining and scored as three grades. Protein expressions of HA synthase 1-3 were examined in the 22 MPNST tissue samples available. Statistically higher HA positivity was observed in MPNST as compared with neurofibroma (P = 0.020). The univariate analysis revealed that increased HA expression, age, neurofibromatosis type 1 (NF1) status, large tumor size, and histological grade were significantly associated with reduced overall survival of patients with MPNST; while increased HA expression, NF1 status, tumor size, and histological grade were correlated with disease-free survival. However, HA synthase 1-3 expression related to neither overall survival nor disease-free survival of these patients. In multivariate analysis, large tumor size (P = 0.022) was an independent prognostic factor for overall survival, and HA expression (P = 0.028) and tumor size (P = 0.002) were independent prognostic factors for disease-free survival. Statistically higher levels of HA in the human MPNST cells were observed compared with neurofibroma cells in vitro. Our results demonstrate that HA expression can be a useful marker in differentiating MPNST from neurofibroma, and in identifying patients with a poor prognosis. Hyaluronan-targeting therapy for patients with MPNST may have potential as a therapeutic tool.
authors: Department of Orthopaedic Surgery, Nagoya University Graduate School and School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.
authors: Kunihiro
authors: K
authors: Ikuta
authors: Hiroshi
authors: H
authors: Urakawa
authors: Eiji
authors: E
authors: Kozawa
authors: Eisuke
authors: E
authors: Arai
authors: Lisheng
authors: L
authors: Zhuo
authors: Naohisa
authors: N
authors: Futamura
authors: Shunsuke
authors: S
authors: Hamada
authors: Koji
authors: K
authors: Kimata
authors: Naoki
authors: N
authors: Ishiguro
authors: Yoshihiro
authors: Y
authors: Nishida
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018317:Nerve Sheath Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D006820:Hyaluronic Acid