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The role of phosphorylated signal transducer and activator of transcription 3 ( pSTAT 3) in peripheral nerve sheath tumours
Author(s) -
Panse Gauri,
Leung Cheuk H,
Ingram Davis R,
Wani Khalida,
Torres Keila E,
Lin Heather,
Lazar Alexander J,
Wang WeiLien
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13154
Subject(s) - medicine , immunohistochemistry , stat protein , cancer research , pathology , stat3 , signal transduction , biology , microbiology and biotechnology
Aims STAT 3 is a pro‐oncogenic transcription factor that requires phosphorylation for transcriptional activation. The aim of this study was to evaluate the role of phosphorylated STAT 3 ( pSTAT 3) expression in neurofibromas, schwannomas, and malignant peripheral nerve sheath tumours ( MPNST s). Methods and Results Twenty‐six neurofibromas, 62 schwannomas and 39 MPNST s from a formalin‐fixed paraffin‐embedded tissue microarray were examined. Immunohistochemical analysis was performed with an anti‐ pSTAT 3 (Tyr705) antibody. Nuclear expression was reviewed for both intensity and percentage of tumoral labelling. Distributions of disease‐specific overall survival ( DSOS ) and event‐free survival ( EFS ) were estimated with the Kaplan–Meier method, and compared between two pSTAT 3 groups by use of the log‐rank test. MPNST s had higher median tumoral labelling than neurofibromas ( P = 0.0012) or schwannomas ( P = 0.0008). Moderate to strong pSTAT 3 expression (defined as at least moderate labelling in ≥50% of cells) was found more frequently in MPNST s than in neurofibromas ( P = 0.026). Among MPNST s, pSTAT 3 expression differed between primary, recurrent and metastatic disease ( P = 0.063 with increased expression in recurrent and metastatic cases). pSTAT 3 expression (at least moderate labelling in ≥10% of cells) in primary MPNST s was associated with worse DSOS ( P = 0.048) and trended towards being associated with worse EFS ( P = 0.063). Paired specimens revealed no increase in pSTAT 3 expression in the recurrences or metastases relative to the primary tumour, suggesting that pSTAT 3 expression may be an early indicator of aggressive disease at disease onset. Conclusions pSTAT 3 is expressed in a higher proportion of MPNST s than neurofibromas and schwannomas. Moderate to strong pSTAT 3 expression in ≥10% of cells was found to be a negative prognostic factor for DSOS among primary MPNST s, suggesting a role of pSTAT 3 in the progression of these tumours.