Abstract
Patients suffering from neurofibromatosis type 1 and 2 (NF1 and NF2) are the main risk groups to develop peripheral nerve sheath tumours (PNSTs). In the present study, adhesion molecules CD34 and podoplanin were assessed in regard to their value for tumour classification and as indicators for tumour progression. A total of 103 NF1-, NF2- and schwannomatosis-associated neurofibromas, schwannomas and malignant peripheral nerve sheath tumours (MPNST), as well as 20 sporadic vestibular schwannomas and 9 control tissue samples, were labelled immunohistochemically for detection of podoplanin and CD34. CD34 was shown to be expressed in MPNST and all benign PNSTs except for the compact cellular parts of both, schwannomas and atypical neurofibromas. Podoplanin showed an inverse expression pattern to CD34 labelling mainly the compact parts of schwannoma and atypical neurofibroma. MPNSTs were characterized by strong podoplanin staining at the invasive front. NF1-patients who suffered from atypical neurofibromas did not develop MPNST at a higher frequency than other NF1-patients, although these tumours expressed podoplanin. Ki-67 proliferation indices did not differ significantly between neurofibromas, atypical neurofibromas and schwannomas. In accordance with other studies, CD34 was found to be of limited value for classification and grading of PNST due to its ubiquitous expression. Podoplanin expression in schwannoma and atypical neurofibroma adds to other phenotypic and genotypic similarities between these tumours, like nuclear atypia, regressive changes and euploid polyploidisation. Podoplanin expression in atypical neurofibroma was not associated with tumour progression towards MPNST.
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References
Nielsen JS, McNagny KM (2008) Novel functions of the CD34 family. J Cell Sci 121:3683–3692
Raica M, Cimpean AM, Ribatti D (2008) The role of podoplanin in tumor progression and metastasis. Anticancer Res 28:2997–3006
Wicki A, Christofori G (2007) The potential role of podoplanin in tumour invasion. Br J Cancer 96:1–5
Hegedus B, Dasgupta B, Shin JE et al (2007) Neurofibromatosis-1 regulates neuronal and glial cell differentiation from neuroglial progenitors in vivo by both cAMP- and Ras-dependent mechanisms. Cell Stem Cell 1:443–457
Ruggieri M (1999) The different forms of neurofibromatosis. A review. Childs Nerv Syst 15:295–308
Xu G, O’Connell P, Viskochil D et al (1990) The Neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 62:599–608
Evans DG, Baser ME, McGaughran J, Sharif S, Howard E, Moran A (2002) Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet 39:311–314
Hagel C, Zils U, Peiper M et al (2007) Histopathology and clinical outcome of NF1-associated sporadic malignant peripheral nerve sheath tumors. J Neurooncol 82:187–192
Ferrari A, Bisogno G, Macaluso A et al (2007) Soft-tissue sarcomas in children and adolescents with neurofibromatosis type 1. Cancer 109:1406–1412
Houshmandi SS, Emnett RJ, Giovannini M, Gutmann DH (2009) The neurofibromatosis 2 protein, Merlin, regulates glial cell growth in an ErbB2- and Src-dependent manner. Mol Cell Biol 29:1472–1486
Trofatter JA, MacCollin MM (1993) A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 72:791–800
Boyd C, Smith MJ, Kluwe L, Balogh A, MacCollin M, Plotkin SR (2008) Alterations in the SMARCB1 (INI1) tumor suppressor gene in familial schwannomatosis. Clin Genet 74:358–366
MacCollin M, Chiocca EA, Evans DG et al (2005) Diagnostic criteria for schwannomatosis. Neurology 64:1838–1845
Gutmann DH, Aylsworth A, Carey JC et al (1997) The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 278:51–57
Stumpf DA, Alksne JF, Annegers JF (1988) Neurofibromatosis NIH consensus development conference statement. Arch Neurol 45:575–578
Baser ME, Evans DGR, Gutmann DH (2003) Neurofibromatosis 2. Curr Opin Neurol 16:27–33
Scheithauer BW, Louis DN, Hunter S, Woodruff JM, Antonescu CR (2007) Neurofibroma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO Classification of tumours of the central nervous system. International Agency for Research on Cancer, Lyon, pp 156–157
Jokinen CH, Dadras SS, Goldblum JR, van de Rijn M, West RB, Rubin BP (2008) Diagnostic implications of podoplanin expression in peripheral nerve sheath neoplasms. Am J Clin Pathol 129:886–893
Drew E, Merzaban JS, Seo W, Ziltener HJ, McNagny KM (2005) CD34 and CD43 inhibit mast cell adhesion and are required for optimal mast cell reconstitution. Immunity 22:43–57
Krause DS, Fackler MJ, Civin CI, May WS (1996) CD34: structure, biology, and clinical utility. Blood 87:1–13
Nielsen JS, McNagny KM (2007) Influence of host irradiation on long-term engraftment by CD34-deficient hematopoietic stem cells. Blood 110:1076–1077
Andrews RG, Singer JW, Bernstein ID (1989) Precursors of colony-forming cells in humans can be distinguished from colony-forming cells by expression of the CD33 and CD34 antigens and light scatter properties. J Exp Med 169:1721–1731
Berenson RJ, Andrews RG, Bensinger WI et al (1988) Antigen CD34+ marrow cells engraft lethally irradiated baboons. J Clin Invest 81:951–955
Ema H, Suda T, Miura Y, Nakauchi H (1990) Colony formation of clone-sorted human hematopoietic progenitors. Blood 75:1941–1946
Fina L, Molgaard HV, Robertson D et al (1990) Expression of the CD34 gene in vascular endothelial cells. Blood 75:2417–2426
Young PE, Baumhueter S, Lasky LA (1995) The sialomucin CD34 is expressed onhematopoietic cells and blood vessels during murine development. Blood 85:96–105
Khalifa MA, Montgomery EA, Ismiil N, Azumi N (2000) What are the CD34+ cells in benign peripheral nerve sheath tumors? Double immunostaining study of CD34 and S-100 protein. Am J Clin Pathol 114:123–126
Tardío JC (2009) CD34-reactive tumors of the skin An updated review of an ever-growing list of lesions. J Cutan Pathol 36:89–102
Weiss SW, Nickoloff BJ (1993) CD34 is expressed by a distinctive cell population in peripheral nerve, nerve sheath tumors, and related lesions. Am J Surg Pathol 17:1039–1045
Kalof AN, Cooper K (2009) D2–40 immunohistochemistry—so far! Adv Anat Pathol 16:62–64
Sonne SB, Herlihy AS, Hoei-Hansen CE et al (2006) Identity of M2A (D2–40) antigen and gp36 (Aggrus, T1α-2, podoplanin) in human developing testis, testicular carcinoma in situ and germ-cell tumours. Virchows Arch 449:200–206
Chu AY, Litzky LA, Pasha TL, Acs G, Zhang PJ (2005) Utility of D2–40, a novel mesothelial marker, in the diagnosis of malignant mesothelioma. Mod Pathol 18:105–110
Martin-Villar E, Scholl FG, Gamallo C et al (2005) Characterization of human PA2.26 antigen (T1alpha-2, podoplanin), a small membrane mucin induced in oral squamous cell carcinomas. Int J Cancer 113:899–910
Wicki A, Lehembre F, Wick N, Hantusch B, Kerjaschki D, Christofori G (2006) Tumor invasion in the absence of epithelial–mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton. Cancer Cell 9:261–272
Valeyrie-Allanore L, Ismaïli N, Bastuji-Garin S et al (2005) Symptoms associated with malignancy of peripheral nerve sheath tumours: a retrospective study of 69 patients with neurofibromatosis 1. Br J Dermatol 153:79–82
Valeyrie-Allanore L, Ortonne N, Lantieri L et al (2008) Histopathologically dysplastic neurofibromas in neurofibromatosis 1: diagnostic criteria, prevalence and clinical significance. Br J Dermatol 158:1008–1012
Mautner VF, Brenner W, Fünsterer C, Hagel C, Gawad K, Friedrich RE (2007) Clinical relevance of positron emission tomography and magnetic resonance imaging in the progression of internal plexiform neurofibroma in NF1. Anticancer Res 27:1819–1822
Brenner W, Friedrich RE, Gawad KA, Hagel C, von Deimling A, de Wit M, Buchert R, Clausen M, Mautner VF (2006) Prognostic relevance of FDG PET in patients with neurofibromatosis type-1 and malignant peripheral nerve sheath tumours. Eur J Nucl Med Mol Imaging 33:428–432
Hruska A, Bollmann R, Kovács RB, Bollmann M, Bodó M, Sápi Z (2004) DNA ploidy and chromosome (FISH) pattern analysis of peripheral nerve sheath tumors. Cell Oncol 26:335–345
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We are grateful to Mr. M. Haberkorn for excellent technical assistance.
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Naber, U., Friedrich, R.E., Glatzel, M. et al. Podoplanin and CD34 in peripheral nerve sheath tumours: focus on neurofibromatosis 1-associated atypical neurofibroma. J Neurooncol 103, 239–245 (2011). https://doi.org/10.1007/s11060-010-0385-4
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DOI: https://doi.org/10.1007/s11060-010-0385-4