Article type: Research Article
Authors: Chiang, Ming-Fu; | Chen, Shur-Tzu | Lo, Chen-Peng | Sze, Chun-I | Chang, Nan-Shan; ; | Chen, Yu-Jen;
Affiliations: Department of Neurosurgery, Mackay Memorial Hospital, Taipei, Taiwan | Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan | Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei, Taiwan | Department of Cell Biology & Anatomy, Nation Cheng Kung University, Tainan, Taiwan | Department of Pathology, University of Colorado Health Sciences Center, Denver, CO, USA | Institute of Molecular Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan | Guthrie Research Institute, Laboratory of Molecular Immunology, Sayre, PA, USA | Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA | Graduate Institute of Pharmacology, Taipei Medical University, Taipei, Taiwan
Note: [] Correspondence to: Nan-Shan Chang, Ph.D., Institute of Molecular Medicine, National Cheng Kung University College of Medicine, 1 University Road, Tainan 7010, Taiwan. Tel.: +886 6 2353535; Fax: +886 6 2751371; E-mail: [email protected]
Note: [] Correspondence to: Yu-Jen Chen, M.D., Ph.D., Department of Radiation Oncology, Mackay Memorial Hospital. 92, Section 2, Chung-Shan North Road, Taipei 104, Taiwan. Tel.: +886 2 910699220; Fax: +886 2 28096180; E-mail: [email protected]
Abstract: BACKGROUND AND OBJECTIVES: We aimed to evaluate the expression levels of the tumor suppressor WOX1 in nervous system tumors and its co-expression with p53 and neurofibromatosis type 2/merlin (NF2) tumor suppressor gene products. METHODS: Immunohistochemistry, western blotting and in situ hybridization were used for WOX1 protein and WWOX mRNA expression. Immunofluorescence and electron microscopical immunohistochemistry were performed for colocalization of gene products. RESULTS: WOX1 expression is low in normal cortical neurons, mainly on the axon fibers, whereas there is moderate to high immunoreactivity in the cytosol and nuclei of certain tumor cells. In the microcystic (WHO grade I) and malignant (WHO grade III) meningiomas, WOX1 expression is intense, but various in transitional (WHO grade I) and atypical (WHO grade II) subtypes. WOX1 levels are moderate to high in the menigiotheliomatous area, but relatively low in the fibroblastic area. WOX1 and NF2/merlin, but not p53, colocalized in certain tumor cells, primarily at the borders of nuclei. Schwannoma and astrocytoma specimens stained moderately to strongly positive for the WOX1 protein. Interestingly, the expression of WOX1, NF2/merlin and mutant p53 is intense in high grade glioblastoma, but WOX1 expression is low in metastatic carcinoma or adenocarcinoma. CONCLUSIONS: The expression of WOX1 on different types of nervous system tumors, including primary and metastatic tumors, is differential.
Keywords: WOX1, NF2/merlin, tumor suppressor gene, meningioma, brain tumors
DOI: 10.3233/ACP-140087
Journal: Analytical Cellular Pathology, vol. 36, no. 5-6, pp. 133-147, 2013
