RETRACTED ARTICLE: Genomic amplification and high expression of EGFR are key targetable oncogenic events in malignant peripheral nerve sheath tumor

Abstract

BackgroundThe dismal outcome of malignant peripheral nerve sheath tumor (MPNST) highlights the necessity of finding new therapeutic methods to benefit patients with this aggressive sarcoma. Our purpose was to investigate epidermal growth factor receptor (EGFR) as a potential therapeutic target in MPNSTs.Patients and methodsWe performed a microarray based-comparative genomic hybridization (aCGH) profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center (MD Anderson) and 26 patients from Tianjin Medical University Cancer Institute & Hospital (TMUCIH). Fluorescence in situ hybridization (FISH) method was used to validate the gene amplification detected by aCGH analysis. Another independent cohort of 56 formalin fixed paraffin embedded (FFPE) MPNST samples was obtained to explore EGFR protein expression by immunohistochemical analysis. Cell biology detection and validation were performed on human MPNST cell lines ST88-14 and STS26T.ResultsaCGH and pathway analysis of the 51 MPNSTs identified significant gene amplification events in EGFR pathway, including frequent amplifications of EGFR gene itself, which was subsequently validated by FISH assay. High expression of EGFR protein was associated with poor disease-free and overall survival of human MPNST patients. In human MPNST cell lines ST88-14 and STS26T, inhibition of EGFR by siRNA or Gefitinib led to decreased cell proliferation, migration, and invasion accompanied by attenuation of PI3K/AKT and MAPK pathways.ConclusionThese results suggest that EGFR is a potential therapeutic target for MPNST.

Morphologic and immunohistochemical features of malignant peripheral nerve sheath tumors and cellular schwannomas

“…In addition, high EGFR expression using a cutoff value of 30% was reported as associated with worse progression-free survival and overall survival rates. 29 In our data set, 5-year disease-specific survival was 35.9 and 25.4% for tumors with and without EGFR expression, respectively, but this did not reach statistical significance. This lack of association with survival remained even when using the 30% cutoff value (data not shown).…”

“…13,24,27 In some studies, EGFR overexpression correlates with more aggressive disease course, advanced stage at presentation, higher tumor mitotic rates, and poor overall outcome. 2,26,29 In this regard, the mean disease-free survival was 17.4 months for patients overexpressing EGFR compared with 30.1 months for patients lacking overexpression, with corresponding 5-year overall survival rates of 25 and 52%, respectively. In addition, high EGFR expression using a cutoff value of 30% was reported as associated with worse progression-free survival and overall survival rates.…”

Malignant Peripheral Nerve Sheath Tumors: From Epigenome to Bedside

“…Many of these trials are evaluating mTOR inhibitors, TK inhibitors, or combination of these treatments. There is preclinical evidence suggesting that such interventions could be effective in MPNST (139)(140)(141)(142)(143)(144)(145)(146)(147), but such data have been poorly predictive of success against MPNST in the past. A candidate therapeutic approach that has been of great recent interest is the application of BET/BRD4 inhibitors.…”

XIAP BIR domain suppresses miR-200a expression and subsequently promotes EGFR protein translation and anchorage-independent growth of bladder cancer cell

“…EGFR overexpression has been widely reported in a number of cancers, including breast, ovarian, bladder, non-small-cell lung (NSCLC), colorectal cancers, and other tumors [23–29]. Aberrant activation or expression of EGFR leads to the promotion of proliferation, cell motility, and invasive capacity of tumor [30–33].…”