Karube K, Nabeshima K, Ishiguro M, Harada M, Iwasaki H
Department of Pathology, School of Medicine, Fukuoka University, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan.
J Clin Pathol. 2006 Feb;59(2):160-5. doi: 10.1136/jcp.2004.023598.
Malignant peripheral nerve sheath tumour (MPNST) is a highly aggressive malignancy that arises within peripheral nerves, and is associated with poor prognosis. Little is known about the underlying biology of MPNST, especially the mechanisms involved in cell proliferation, invasion, or escape from apoptosis.
To identify genes differentially expressed in MPNST compared with benign tumours, such as neurofibromas and schwannomas, by means of cDNA microarray analysis.
Six MPNST cases and five benign cases (three schwannomas and two neurofibromas) were analysed.
Six genes (keratin 18, survivin, tenascin C, adenosine deaminase, collagen type VIa3, and collagen type VIIa1) were significantly upregulated in MPNST, whereas one gene, insulin-like growth factor binding protein 6, was downregulated in MPNST. Survivin and tenascin C expression was validated by reverse transcription polymerase chain reaction. Immunohistochemistry confirmed upregulation of survivin in MPNST at the protein level in six of eight cases compared with benign tumours. Tenascin C was also expressed at the invasive front and tumorous stroma in all MPNST cases. MPNST cells expressed tenascin C in four of nine cases.
Survivin and tenascin C may be associated with the malignant potential of MPNST and could be considered as potential therapeutic targets.
恶性外周神经鞘瘤（MPNST）是一种起源于外周神经的高度侵袭性恶性肿瘤，预后较差。关于MPNST的潜在生物学特性，尤其是细胞增殖、侵袭或逃避凋亡所涉及的机制，人们了解甚少。
通过cDNA微阵列分析，鉴定与良性肿瘤（如神经纤维瘤和神经鞘瘤）相比，MPNST中差异表达的基因。
分析6例MPNST病例和5例良性病例（3例神经鞘瘤和2例神经纤维瘤）。
6个基因（角蛋白18、生存素、腱生蛋白C、腺苷脱氨酶、Ⅵa3型胶原蛋白和Ⅶa1型胶原蛋白）在MPNST中显著上调，而1个基因胰岛素样生长因子结合蛋白6在MPNST中下调。通过逆转录聚合酶链反应验证了生存素和腱生蛋白C的表达。免疫组织化学证实，与良性肿瘤相比，8例中有6例MPNST中生存素在蛋白水平上调。所有MPNST病例中，腱生蛋白C也在侵袭前沿和肿瘤基质中表达。9例中有4例MPNST细胞表达腱生蛋白C。
生存素和腱生蛋白C可能与MPNST的恶性潜能相关，可被视为潜在的治疗靶点。
