Research Papers:

This article has been corrected. Correction in: Oncotarget. 2021; 12:2435-2436.

Aberrant ATRX protein expression is associated with poor overall survival in NF1-MPNST

Hsiang-Chih Lu, Vanessa Eulo, Anthony J. Apicelli, Melike Pekmezci, Yu Tao, Jingqin Luo, Angela C. Hirbe _ and Sonika Dahiya _

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Oncotarget. 2018; 9:23018-23028. https://doi.org/10.18632/oncotarget.25195

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Hsiang-Chih Lu1,*, Vanessa Eulo2,*, Anthony J. Apicelli3,4, Melike Pekmezci5, Yu Tao6, Jingqin Luo6, Angela C. Hirbe7,4 and Sonika Dahiya1,4

1 Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA

2 Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

3 Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA

4 Siteman Cancer Center, Washington University School of Medicine, Saint Louis, MO, USA

5 Department of Pathology, University of California San Francisco School of Medicine, San Francisco, CA, USA

6 Siteman Cancer Center Biostatistics Shared Resource, Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA

7 Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA

* Co-first authors

Correspondence to:

Sonika Dahiya, email: [email protected]
Angela C. Hirbe, email: [email protected]

Keywords: neurofibromatosis; MPNST; plexiform neurofibroma; atypical neurofibroma; ATRX

Received: December 26, 2017     Accepted: April 06, 2018     Published: May 01, 2018


Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive soft tissue sarcomas that can occur sporadically or in the setting of the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. These tumors carry a dismal overall survival. Previous work in our lab had identified ATRX chromatin remodeler (ATRX), previously termed, Alpha Thalassemia/Mental Retardation Syndrome X Linked as a gene mutated in a subset of MPNSTs. Given the great need for novel biomarkers and therapeutic targets for MPNSTs, we sought to determine the expression of ATRX in a larger subset of sporadic and NF1 associated MPNSTs (NF1-MPNSTs). We performed immunohistochemistry (IHC) on 74 MPNSTs (43 NF1-associated and 31 sporadic), 21 plexiform neurofibromas, and 9 atypical neurofibromas. Using this approach, we have demonstrated that 58% (43/74) of MPNSTs have aberrant ATRX expression (<80% nuclear expression) compared to only 7% (2/30) of benign (plexiform and atypical) neurofibromas. Second, we demonstrated that 65% (28/43) of NF1-MPNSTs displayed aberrant ATRX expression as did 48% (15/31) of sporadic MPNSTs. Finally, we show that aberrant ATRX expression was associated with a significantly decreased overall survival for patients with NF1-MPNST (median OS of 17.9 months for aberrant expression and median OS not met (>120 months) for intact expression, p = 0.0276). In summary, we demonstrate that ATRX is aberrantly expressed in the majority of NF1-MPNSTs, but not plexiform or atypical neurofibromas. Additionally, aberrant ATRX expression is associated with decreased overall survival in NF1-MPNST, but not sporadic MPNST and may serve as a prognostic marker for patients with NF1-MPNST.

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