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Clinicopathological Features and HOX Transcript Antisense RNA In Situ Hybridization Detection of Myxopapillary Ependymoma
ZHANGYuhan, WANGZheng, LUJunliang, ZHAODachun, HUOZhen
Acta Academiae Medicinae Sinicae ›› 2025, Vol. 47 ›› Issue (1) : 35-41.
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Abbreviation (ISO4): Acta Academiae Medicinae Sinicae
Editor in chief: Xuetao CAO
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Clinicopathological Features and HOX Transcript Antisense RNA In Situ Hybridization Detection of Myxopapillary Ependymoma
Objective To summarize the clinicopathological features,immunohistochemical characteristics,HOX transcript antisense RNA(HOTAIR)in situ hybridization status,treatment,and prognosis of myxopapillary ependymoma(MPE). Methods A total of 17 patients diagnosed with MPE based on pathological evidence in the Department of Pathology of Peking Union Medical College Hospital from November 2006 to July 2023 were selected,and the clinicopathological data of these patients were collected.Immunohistochemical staining for trimethylation at lysine 27 of histone H3 (H3K27me3),glial fibrillary acidic protein(GFAP),and epithelial membrane antigen(EMA)and alcian blue-periodic acid Schiff(AB-PAS)staining were performed in all the patients.Sixteen patients with spinal ependymomas were selected as the control group.Tissue microarrays were prepared from 17 MPE patients and the control group.HOTAIR ISH was performed and semi-quantitatively scored,and the scores of the two groups were compared by the Wilcoxon rank-sum test. Results The 17 MPE patients aged 14-64 years,with the mean age of(37.48±16.10)years and the male-to-female ratio of 0.7∶1.Their clinical manifestations mainly included lumbosacral and lower limb pains.Microscopically,tumor cells were arranged in a papillary pattern around fibrovascular axis,with abundant myxoid materials,and tumor cells were arranged in a loose meshwork in some patients.The immunohistochemical staining results showed that 17(100%),10(58.82%),and 8(47.06%)patients expressed GFAP,EMA,and D2-40,respectively,and 2(11.76%)patients lacked expression of H3K27me3.AB-PAS staining showed blue myxoid materials in all the 17(100%)patients.HOTAIR was expressed in both MPE and control groups,with higher semi-quantitative score in the MPE group than in the control group(P=0.004).Twelve patients were followed up,with a median follow-up period of 65.50 months,during which three patients showed recurrence.Conclusions MPE exhibits typical pathological features,and the combination with immunohistochemical staining for GFAP and EMA as well as AB-PAS staining facilitates diagnosis of this disease.A small number of patients loss the expression of H3K27me3.HOTAIR is highly expressed in MPE but lacks specificity,which limits its auxiliary diagnostic value.The overall prognosis of MPE is favorable,with a few patients experiencing recurrence.
myxopapillary ependymoma / clinicopathological features / trimethylation at lysine 27 of histone H3 / HOX transcript antisense RNA
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We report the differential clinicopathologic and immunophenotypical features of 2 pure ovarian ependymomas of extra-axial type with a predominant microcystic, anaplastic pattern occurring in patients aged 22 and 32 years and a unique myxopapillary pigmented ependymoma that originated within an ovarian mature cystic teratoma in a 35-year-old woman. The latter had a central nervous system phenotype different from that previously reported in ovarian ependymomas of extra-axial types, being negative for estrogen and progesterone receptors, epithelial membrane antigen and cytokeratin 34βE12, cell adhesion molecule 5.2, and cytokeratin 7. Furthermore, its benign behavior contrasted with the aggressive course of the other 2 ependymomas of extra-axial types, in which peritoneal invasion was present at the time of diagnosis. These findings illustrate that both central and extra-axial types of ependymoma show phenotypic variations that may point to either a derivation from different precursors or differentiation along diverse pathways. Thus, whereas ependymomas of extra-axial types would represent neometaplastic phenomena, those originated from the nervous tissue of teratomas resemble central nervous system ependymomas. Moreover, the dissimilarities between central and peripheral types of ependymoma would parallel the phenotypic differences present in primitive neural tumors of the female genital tract.Copyright © 2011 Elsevier Inc. All rights reserved.
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Posterior fossa ependymomas (EPN_PF) in children comprise two morphologically identical, but biologically distinct tumor entities. Group-A (EPN_PFA) tumors have a poor prognosis and require intensive therapy. In contrast, group-B tumors (EPN_PFB) exhibit excellent prognosis and the current consensus opinion recommends future clinical trials to test the possibility of treatment de-escalation in these patients. Therefore, distinguishing these two tumor subtypes is critical. EPN_PFA and EPN_PFB can be distinguished based on DNA methylation signatures, but these assays are not routinely available. We have previously shown that a subset of poorly prognostic childhood EPN_PF exhibits global reduction in H3K27me3. Therefore, we set out to determine whether a simple immunohistochemical assay for H3K27me3 could be used to segregate EPN_PFA from EPN_PFB tumors. We assembled a cohort of 230 childhood ependymomas and H3K27me3 immunohistochemistry was assessed as positive or negative in a blinded manner. H3K27me3 staining results were compared with DNA methylation-based subgroup information available in 112 samples [EPN_PFA (n = 72) and EPN_PFB tumors (n = 40)]. H3K27me3 staining was globally reduced in EPN_PFA tumors and immunohistochemistry showed 99% sensitivity and 100% specificity in segregating EPN_PFA from EPN_PFB tumors. Moreover, H3K27me3 immunostaining was sufficient to delineate patients with worse prognosis in two independent, non-overlapping cohorts (n = 133 and n = 97). In conclusion, immunohistochemical evaluation of H3K27me3 global reduction is an economic, easily available and readily adaptable method for defining high-risk EPN_PFA from low-risk posterior fossa EPN_PFB tumors to inform prognosis and to enable the design of future clinical trials.
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