Prognostic Significance of Immunohistochemical Markers and Genetic Alterations in Malignant Peripheral Nerve Sheath Tumors: A Systematic Review

Abstract

BackgroundMalignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas with dismal prognosis. Pathological and genetic markers may predict more aggressive behavior in MPNSTs but have uncommonly been investigated, and few are used in daily practice. This study reviews the prognostic value of immunohistochemical markers and genetic alterations in MPNST.MethodsA systematic search was performed in PubMed and Embase databases according to the PRISMA guidelines. Search terms related to ‘MPNST’ and ‘prognostic’ were used. Studies investigating the association of immunohistochemical markers or genetic alterations with prognosis were included. Qualitative synthesis was performed on all studies. A distinction was made between univariable and multivariable associations.ResultsForty-six studies were included after full-text screening. Sixty-seven different immunohistochemical markers were investigated. Absence of S100 and H3K27me3 and high Ki67 and p53 staining was most commonly independently associated with worse survival and disease-free survival. Several genetic alterations were investigated as well with varying association to survival. TP53, CDK4, RASSF1A alterations were independently associated with worse survival, as well as changes in chromosomal length in Xp, 10q, and 16p.ConclusionsMPNSTs harbor complex and heterogeneous biology. Immunohistochemical markers and genetic alterations have variable prognostic value. Absence of S100 and H3K27me3 and increased Ki67 can be of prognostic value. Alterations in TP53 or increase in p53 staining may distinguish MPNSTs with worse outcomes. Genetic alterations and staining of other cell cycle regulatory and Ras pathway proteins may also help stratifying patients with worse outcomes. A combination of markers can increase the prognostic value.

Survival and NF1 Analysis in a Cohort of Orthopedics Patients with Malignant Peripheral Nerve Sheath Tumors

“…Consistent with previous reports, we noted that subjects with S100B-positive tumors had significantly better outcomes than those with S100B-negative tumors [ 12 ]. S100 B is a mature Schwann-cell protein, and loss of immunostaining is consistent with poorer cell differentiation.…”

“…Adjuvant radiation or chemotherapy regimens have also been used at different institutions to reduce the risk of local recurrence or to treat systemic disease [ 7 ]. Although recent trials with novel targeted therapies have so far proven ineffective, recurrent gene mutations that have been associated with more aggressive tumors in patients with NF1, such as the polycomb repressive complex 2 (PRC2) core components, embryonic ectoderm development protein (EED), and suppressor of zeste 12 homolog (SUZ12), may serve as future treatment targets [ 9 – 12 ]. There is some controversy in the literature regarding germline NF1 mutation effect on the risk of developing an MPNST.…”

Histopathological and Immunohistochemical Evaluation of Canine Nerve Sheath Tumors and Proposal for an Updated Classification

“…We used a high Ki-67 proliferation index as an indicator of malignancy because it has been described as an important prognostic indicator in humans, with an elevated index indicating a worse prognosis [ 17 , 31 , 32 ]. However, caution should be taken not to diagnose the tumor as malignant too quickly, as Ki-67 values of MNSTs and cellular schwannomas may overlap.…”

Malignant peripheral nerve sheath tumour of the oral and maxillofacial region—A systematic review

“…Herein, S100 was positive in 33 cases and negative in four cases. The absence of S100 staining has been defined as one of the most common independent features associated with worse disease‐free survival (Martin et al, 2020). Among the cases retrieved herein, three S100‐negative individuals had follow‐up information.…”

“…as one of the most common independent features associated with worse disease-free survival (Martin et al, 2020). Among the cases retrieved herein, three S100-negative individuals had follow-up information.…”