Clinical and molecular prognostic predictors of malignant peripheral nerve sheath tumor
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Malignant peripheral nerve sheath tumors (MPNST) are relatively rare sarcomas and poorly understood. We sought to find clinicopathological and molecular predictors of survival for Chinese MPNST patients.
Clinical information from 146 MPNST patients treated in the Tianjin Medical University Cancer Institute and Hospital was collected and 56 cases of formalin-fixed and paraffin-embedded tissues were available for immunohistochemical examination of expression of hepatocyte growth factor receptor (c-MET), E3 ubiquitin-protein ligase Mdm2 (MDM2), and TP53.
The 5-year tumor-free survival rate was 24 % and the median tumor-free survival time was 25.64 months. The 5-year overall survival rate was 57 % and the median overall survival time was 132.57 months. The expression patterns of c-MET, TP53, and MDM2 were heterogeneous with total positivity rates of 82.1 % (46/56), 55.4 % (31/56), and 73.2 % (41/56), respectively. The univariate analysis not only showed that tumor size, Neurofibromin 1 (NF1) status, the American Joint Committee on Cancer (AJCC) stage, surgery, MDM2 expression, and TP53 expression had significant correlation with the tumor-free survival, but also demonstrated that radiotherapy, chemotherapy, tumor size, and NF1 status had significant correlation with the overall survival. Even though multivariate analysis found no independent prognostic predictor of MPNST, tumor size and NF1 status had significant correlation with the tumor-free survival and overall survival of MPNST patients.
With this, the largest documented Chinese cohort, our data supply powerful Chinese evidence of the prognostic role of tumor size and NF1 status in MPNST.
- Gupta G, Mammis A, Maniker A. Malignant peripheral nerve sheath tumors. Neurosurg Clin N Am. 2008;19(4):533–43. CrossRef
- Fuchs B, Spinner RJ, Rock MG. Malignant peripheral nerve sheath tumors: an update. J Surg Orthop Adv. 2005;14(4):168–74.
- Wanebo JE, Malik JM, VandenBerg SR, Wanebo HJ, Driesen N, Persing JA. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 28 cases. Cancer. 1993;71(4):1247–53. CrossRef
- Gupta G, Maniker A. Malignant peripheral nerve sheath tumors. Neurosurg Focus. 2007;22(6):E12. CrossRef
- Grobmyer SR, Reith JD, Shahlaee A, Bush CH, Hochwald SN. Malignant peripheral nerve sheath tumor: molecular pathogenesis and current management considerations. J Surg Oncol. 2008;97(4):340–9. CrossRef
- Hagel C, Zils U, Peiper M, Kluwe L, Gotthard S, Friedrich RE, et al. Histopathology and clinical outcome of NF1-associated vs. sporadic malignant peripheral nerve sheath tumors. J Neurooncol. 2007;82(2):187–92. CrossRef
- Anghileri M, Miceli R, Fiore M, Mariani L, Ferrari A, Mussi C, et al. Malignant peripheral nerve sheath tumors: prognostic factors and survival in a series of patients treated at a single institution. Cancer. 2006;107(5):1065–74. CrossRef
- Zou C, Smith KD, Liu J, Lahat G, Myers S, Wang WL, et al. Clinical, pathological, and molecular variables predictive of malignant peripheral nerve sheath tumor outcome. Ann Surg. 2009;249(6):1014–22. CrossRef
- Okada K, Hasegawa T, Tajino T, Hotta T, Yanagisawa M, Osanai T, et al. Clinical relevance of pathological grades of malignant peripheral nerve sheath tumor: a multi-institution TMTS study of 56 cases in Northern Japan. Ann Surg Oncol. 2007;14(2):597–604. CrossRef
- Kar M, Deo SV, Shukla NK, Malik A, DattaGupta S, Mohanti BK, et al. Malignant peripheral nerve sheath tumors (MPNST)—clinicopathological study and treatment outcome of twenty-four cases. World J Surg Oncol. 2006;4:55. CrossRef
- Carli M, Ferrari A, Mattke A, Zanetti I, Casanova M, Bisogno G, et al. Pediatric malignant peripheral nerve sheath tumor: the Italian and German soft tissue sarcoma cooperative group. J Clin Oncol. 2005;23(33):8422–30. CrossRef
- Yang J, Ylipaa A, Sun Y, Zheng H, Chen K, Nykter M, et al. Genomic and molecular characterization of malignant peripheral nerve sheath tumor identifies the IGF1R pathway as a primary target for treatment. Clin Cancer Res. 2011;17(24):7563–73. CrossRef
- Kindblom LG, Ahlden M, Meis-Kindblom JM, Stenman G. Immunohistochemical and molecular analysis of p53, MDM2, proliferating cell nuclear antigen and Ki67 in benign and malignant peripheral nerve sheath tumours. Virchows Arch. 1995;427(1):19–26. CrossRef
- Watanabe T, Oda Y, Tamiya S, Masuda K, Tsuneyoshi M. Malignant peripheral nerve sheath tumour arising within neurofibroma. An immunohistochemical analysis in the comparison between benign and malignant components. J Clin Pathol. 2001;54(8):631–6. CrossRef
- Watanabe T, Oda Y, Tamiya S, Kinukawa N, Masuda K, Tsuneyoshi M. Malignant peripheral nerve sheath tumours: high Ki67 labelling index is the significant prognostic indicator. Histopathology. 2001;39(2):187–97. CrossRef
- Holtkamp N, Atallah I, Okuducu AF, Mucha J, Hartmann C, Mautner VF, et al. MMP-13 and p53 in the progression of malignant peripheral nerve sheath tumors. Neoplasia. 2007;9(8):671–7. CrossRef
- Yang J, Yang D, Sun Y, Sun B, Wang G, Trent JC, et al. Genetic amplification of the vascular endothelial growth factor (VEGF) pathway genes, including VEGFA, in human osteosarcoma. Cancer. 2011;117(21):4925–38. CrossRef
- Tabone-Eglinger S, Bahleda R, Cote JF, Terrier P, Vidaud D, Cayre A, et al. Frequent EGFR positivity and overexpression in high-grade areas of human MPNSTs. Sarcoma. 2008;2008:849156. CrossRef
- Brekke HR, Kolberg M, Skotheim RI, Hall KS, Bjerkehagen B, Risberg B, et al. Identification of p53 as a strong predictor of survival for patients with malignant peripheral nerve sheath tumors. Neuro Oncol. 2009;11(5):514–28. CrossRef
- Itahana K, Mao H, Jin A, Itahana Y, Clegg HV, Lindstrom MS, et al. Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation. Cancer Cell. 2007;12(4):355–66. CrossRef
- Clegg HV, Itahana K, Zhang Y. Unlocking the Mdm2-p53 loop: ubiquitin is the key. Cell Cycle. 2008;7(3):287–92. CrossRef
- Szadowska A, Olborski B, Harezga-Bal B, Debiec-Rychter M. Expression of P53, MDM2 and Ki-67 antigens in soft tissue sarcomas. Pol J Pathol: Off J Pol Soc Pathol. 1999;50(1):9–16.
- Su W, Gutmann DH, Perry A, Abounader R, Laterra J, Sherman LS. CD44-independent hepatocyte growth factor/c-Met autocrine loop promotes malignant peripheral nerve sheath tumor cell invasion in vitro. Glia. 2004;45(3):297–306. CrossRef
- Mantripragada KK, Spurlock G, Kluwe L, Chuzhanova N, Ferner RE, Frayling IM, et al. High-resolution DNA copy number profiling of malignant peripheral nerve sheath tumors using targeted microarray-based comparative genomic hybridization. Clin Cancer Res. 2008;14(4):1015–24. CrossRef
- Minovi A, Basten O, Hunter B, Draf W, Bockmuhl U. Malignant peripheral nerve sheath tumors of the head and neck: management of 10 cases and literature review. Head Neck. 2007;29(5):439–45. CrossRef
- Ardern-Holmes SL, North KN. Therapeutics for childhood neurofibromatosis type 1 and type 2. Curr Treat Options Neurol. 2011;13(6):529–43. CrossRef
- Ferrari A, Bisogno G, Carli M. Management of childhood malignant peripheral nerve sheath tumor. Paediatr Drugs. 2007;9(4):239–48. CrossRef
- Wong WW, Hirose T, Scheithauer BW, Schild SE, Gunderson LL. Malignant peripheral nerve sheath tumor: analysis of treatment outcome. Int J Radiat Oncol Biol Phys. 1998;42(2):351–60. CrossRef
- Clinical and molecular prognostic predictors of malignant peripheral nerve sheath tumor
Clinical and Translational Oncology
Volume 16, Issue 2 , pp 191-199
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- Malignant peripheral nerve sheath tumor
- Neurofibromatosis 1
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