H3K27me3 Is A Highly Sensitive Marker For MPNST

PurposeMalignant peripheral nerve sheath tumors(MPNST)are rare neoplasms occurring mostly in adults and representing approximately 4% of all sarcomas.About 50% of MPNSTs occur in patients afflicted by type 1 neurofibromatosis(NF1),whereas about 10% of cases arise secondary to prior radiotherapy(RT).The remaining 40% of cases occur without known predisposition.MPNST are with highly grade malignancy and relapse rate,also metastasis ability are very strong.The diagnosis of MPNST remains challenging and somewhat arbitrary because of its nonspecific morphologic features and lack of pathognomonic ancillary IHC and molecular diagnostic markers.The N-terminal lysine residue K27 is one of the major methylation modification sites and the extent of methylation can affect the transcriptional activity of DNA in the corresponding region.H3K27me3 is frequently expression loss in non-NF1 MPNST.H3K27me3 is very promising as an important biomarker for the diagnosis of MPNST.To investigate the expression and prognostic effect of H3K27me3 in malignant peripheral nerve sheath tumor MPNST with tissue microarray TMA technique,immunohistochemistry andcytology method.MethodA total of 43 MPNST patients from Tianjin Medical University Cancer Institute and Hospital were enrolled in this study from 1991.1 to 2011.11.Tissue microarray(TMA)technique and immunohistochemistry(IHC)method were used for H3K27me3 immunostaining.Clinicopathologic and suvival data were carefully collected.Western blotting verification of intracellular H3K27me3 expression in MPNST cells.The relation of H3K27me3 different expression levels with clinical feature and prognosis of patients was compared by SPSS 19.0.The relationship between the expression of H3K27me3 and clinicopathological parameters was tested by Chi-square test or Fisher's exact test.The differencewasstatisticallysignificantatP<0.05.Result1.The quality of TMAwas perfect and meet the standard of analysis.Among all MPNST patients.65.11% were characterized with loss expression of H3K27me3,39.53% were complete loss and 25.58% werepartial loss expression ofH3K27me3.If loss expression of H3K27me3 was a diagnostic basis of MPNST,the detectable rate was 65.11%,in keepingwithoriginaldiagnostic.2.Among the 39 sporadic MPNST patients,43.58% complete loss expression of H3K27me3,and the partial loss patients were 28.20%.All of The type 1 neurofibromatosis(NF1)MPNSTs expressed H3K27me3.The detectable rate was 71.78% outside of NF1 clinicalhistoryMPNST.3.The expression level of H3K27me3 was not associated with sex,age,tumor size,AJCC grade,radiotherapy and chemotherapy,recurrence and metastasis,but was closely relatedtowhetherMPNSTwasNF1type(P= 0.014).4.In the MPNST cell lines ST88-14 and STS26 T,intracellular protein was extracted and subjected to Western blotting.As a result,it was found that the expression of H3K27me3 in the malignant peripheral nerve sheath tumor cells was significantly lower than that of the control group,indicatingthatPart ofthecellexpression is missing.ConclusionThe present study verified the expression of H3K27me3 in MPNST,and that H3K27me3 is absent in most malignant peripheral nerve sheath tumours(including complete loss of expression and the expression part is missing),and if the loss of expression of H3K27me3 is used as a diagnostic indicator of MPNST,it has good sensitivity and specificity.The protein expression level of H3K27me3 was not associated with the onset gender,age,tumor size,AJCC grade,radiochemotherapy,recurrence and metastasis of MPNST,but it was closely related tothe typeof malignant peripheralnerve sheath tumors that wererelated toNF1.The relationship,in the preclinical diagnosis of malignant peripheral schwannoma in a NF1-related clinical context,has a more important significance,and is expected to become a biological marker for the early diagnosis of non-NF1-related malignant peripheral nerve sheath tumors.