Journal of Pathology and Translational Medicine

Original Articles

Protein Phosphatase Magnesium-Dependent 1δ (PPM1D) Expression as a Prognostic Marker in Adult Supratentorial Diffuse Astrocytic and Oligodendroglial Tumors: Hui Jeong Jeong, Chang Gok Woo, Bora Lee, Shin Kwang Khang, Soo Jeong Nam, Jene Choi; J Pathol Transl Med. 2018;52(2):71-78. Published online October 18, 2017; DOI: https://doi.org/10.4132/jptm.2017.10.21

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Background
Protein phosphatase magnesium-dependent 1δ (PPM1D) is a p53-induced serine/ threonine phosphatase, which is overexpressed in various human cancers. A recent study reported that a mutation in the PPM1D gene is associated with poor prognosis in brainstem gliomas. In this study, we evaluated the utility of PPM1D as a prognostic biomarker of adult supratentorial diffuse astrocytic and oligodendroglial tumors.
Methods
To investigate PPM1D protein expression, mRNA expression, and copy number changes, immunohistochemistry, RNAscope in situ hybridization, and fluorescence in situ hybridization were performed in 84 adult supratentorial diffuse gliomas. We further analyzed clinical characteristics and overall survival (OS) according to PPM1D protein expression, and examined its correlation with other glioma biomarkers such as isocitrate dehydrogenase (IDH) mutation, and p53 expression.
Results
Forty-six cases (54.8%) were PPM1D-positive. PPM1D expression levels were significantly correlated with PPM1D transcript levels (p= .035), but marginally with PPM1D gene amplification (p=.079). Patients with high-grade gliomas showed a higher frequency of PPM1D expression than those with low-grade gliomas (p <.001). Multivariate analysis demonstrated that PPM1D expression (hazard ratio [HR], 2.58; p=.032), age over 60 years (HR, 2.55; p=.018), and IDH1 mutation (HR, 0.18; p=.002) were significantly independent prognostic factors; p53 expression had no prognostic significance (p=.986). The patients with tumor expressing PPM1D showed a shorter OS (p=.003). Moreover, patients with tumor harboring wild-type IDH1 and PPM1D expression had the worst OS (p<.001).
Conclusions
Our data suggest that a subset of gliomas express PPM1D; PPM1D expression is a significant marker of poor prognosis in adult supratentorial diffuse astrocytic and oligodendroglial tumors.

Citations

Citations to this article as recorded by

Characteristic analysis and identification of novel molecular biomarkers in elderly glioblastoma patients using the 2021 WHO Classification of Central Nervous System Tumors
Yaning Wang, Junlin Li, Yaning Cao, Wenlin Chen, Hao Xing, Xiaopeng Guo, Yixin Shi, Yuekun Wang, Tingyu Liang, Liguo Ye, Delin Liu, Tianrui Yang, Yu Wang, Wenbin Ma
Frontiers in Neuroscience.2023;[Epub] CrossRef
Metal-dependent Ser/Thr protein phosphatase PPM family: Evolution, structures, diseases and inhibitors
Rui Kamada, Fuki Kudoh, Shogo Ito, Itsumi Tani, Jose Isagani B. Janairo, James G. Omichinski, Kazuyasu Sakaguchi
Pharmacology & Therapeutics.2020; 215: 107622. CrossRef

Diagnostic Significance of Cellular Neuroglial Tissue in Ovarian Immature Teratoma: Yun Chai, Chang Gok Woo, Joo-Young Kim, Chong Jai Kim, Shin Kwang Khang, Jiyoon Kim, In Ah Park, Eun Na Kim, Kyu-Rae Kim; J Pathol Transl Med. 2017;51(1):49-55. Published online October 14, 2016; DOI: https://doi.org/10.4132/jptm.2016.09.19

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Abstract PDF

Background
Immature teratoma (IT) is a tumor containing immature neuroectodermal tissue, primarily in the form of neuroepithelial tubules. However, the diagnosis of tumors containing only cellular neuroglial tissue (CNT) without distinct neuroepithelial tubules is often difficult, since the histological characteristics of immature neuroectodermal tissues remain unclear. Here, we examined the significance of CNT and tried to define immature neuroectodermal tissues by comparing the histological features of neuroglial tissues between mature teratoma (MT) and IT.
Methods
The histological features of neuroglial tissue, including the cellularity, border between the neuroglial and adjacent tissues, cellular composition, mitotic index, Ki-67 proliferation rate, presence or absence of tissue necrosis, vascularity, and endothelial hyperplasia, were compared between 91 MT and 35 IT cases.
Results
CNTs with a cellularity grade of ≥ 2 were observed in 96% of IT cases and 4% of MT cases (p < .001); however, CNT with a cellularity grade of 3 in MT cases was confined to the histologically distinct granular layer of mature cerebellar tissue. Moreover, CNT in IT exhibited significantly higher rates of Ki-67 proliferation, mitoses, and necrosis than those in MT (p < .001). Furthermore, an infiltrative border of neuroglial tissue and glomeruloid endothelial hyperplasia were significantly more frequent in IT cases than in MT cases (p < .001).
Conclusions
Our results suggest that if CNT with a cellularity grade of ≥ 2 is not a component of cerebellar tissue, such cases should be diagnosed as IT containing immature neuroectodermal tissue, particularly if they exhibit an infiltrative border, mitoses, necrosis, and increased Ki-67 proliferation.

Citations

Citations to this article as recorded by

An Atypical Presentation of a Pediatric Mature Teratoma: A Case Report and Review of the Literature
Ahmed M Othman, Abdulaziz A Abu Alnasr, Reem E Kordi, Shahad A Abu Alnasr
Cureus.2024;[Epub] CrossRef
Immature Teratoma: Diagnosis and Management—A Review of the Literature
Liviu Moraru, Melinda-Ildiko Mitranovici, Diana Maria Chiorean, Marius Coroș, Raluca Moraru, Ioan Emilian Oală, Sabin Gligore Turdean
Diagnostics.2023; 13(9): 1516. CrossRef
Congenital Immature Grade ΙΙΙ Teratoma of the Neck: A Case Report
Nazneen Liaqat, Israr Ud Din, Zeeshan Ali, Majid Rashid, Afsheen Liaqat
Cureus.2023;[Epub] CrossRef
Benign ovarian teratoma in the dog with predominantly nervous tissue: A case report
P Makovicky, AV Makarevich, P Makovicky, A Seidavi, L Vannucci, K Rimarova
Veterinární medicína.2022; 67(2): 99. CrossRef
Fascin as a Useful Marker for Identifying Neural Components in Immature Teratomas of Human Ovary and Those Derived From Murine Embryonic Stem Cells
Ryunosuke Umehara, Atsushi Kurata, Masakatsu Takanashi, Hirotsugu Hashimoto, Koji Fujita, Toshitaka Nagao, Masahiko Kuroda
International Journal of Gynecological Pathology.2019; 38(4): 377. CrossRef
Cerebellar Differentiation in Ovarian Teratoma: A Report of 6 Cases
Colin J.R. Stewart, Maxine L. Crook
International Journal of Gynecological Pathology.2018; 37(4): 316. CrossRef
Mitotic activity of epithelia of ectoand entodermal types in spontaneous and experimental teratomas of mice
Pavel A. Dyban
Medical academic journal.2018; 18(4): 42. CrossRef
Ovarian cystectomy in the treatment of apparent early-stage immature teratoma
Ting Zhao, Yan Liu, Xiao Wang, Hao Zhang, Yuan Lu
Journal of International Medical Research.2017; 45(2): 771. CrossRef

Expression of c-fos, p53, Transforming Growth Factor-beta1 and Glial Fibrillary Acidic Protein in Hippocampus Following Transient Forebrain Ischemia in Mongolian Gerbil.: Jae Hwa Lee, Bang Hur; Korean J Pathol. 2001;35(1):60-70.

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Abstract PDF: BACKGROUND
Recent studies have shown that delayed neuronal death is closely associated with early gene (c-fos or c-jun)-related apoptosis in addition to hypoxia-induced energy deficiency in the hippocampus.
METHODS
To elucidate the role of c-fos, p53, TGF-1 and glial fibrillary acidic protein (GFAP) and their interactions, cellular expression with immunohistochemistry was examined during the time period of 10-minute hypoxia with variable reperfusion intervals in the mongolian gerbil hippocampus.
RESULTS
Hippocampal CA1 shows progressive and delayed neuronal damage beginning from the 24-hour reperfusion, while CA2-3 reveals non-progressive, eosinophilic inclusion body within the neuron throughout the time period. CA1 neurons show short-term expressions of c-fos prior to significant cellular damage. However, CA2-3 neurons show persistent expressions by 3-day reperfusion. In both CA1 and CA2-3, p53 is expressed for the short-term period of the early time points. However, its intensity and duration are much less in CA2-3 than in CA1. While TGF-1 is transiently expressed at 24-hour reperfusion in CA1, its expression in CA2-3 is persistent in late time points. Early expression of GFAP is observed in the pyramidal layer of CA1 prior to neuronal damage and progressively increased in the late time points.
CONCLUSION
These results suggest that c-fos and TGF-1 may play a role in neuronal viability in the early- and late time points. Astrocytes may also be responsible for the active protective mechanism to neuronal death, as well as reactive gliosis. The hypoxia-induced neuronal damage is, in part, a p53-dependent process in the CA1 neurons.

Case Report

Glial Choristoma of the Middle Ear: A Case Report.: Su Jin Kim, Dae Cheol Kim; Korean J Pathol. 2007;41(5):362-365.

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Abstract PDF: Glial choristoma is defined as a mass that is composed of mature, normal brain tissue, isolated from the cranial cavity or spinal canal. The involvement of an extracranial non-midline location, especially the middle ear or mastoid region, is quite exceptional. We report here on a case of glial choristoma of the middle ear in a 2-year-old boy. He presented with otalgia and otorrhea that had lasted for 6 months, and radiological studies revealed a mass-like lesion with soft tissue density in the middle ear cavity. The patient underwent simple mastoidectomy and tympanoplasty. Histologically, the mass was composed of disorganized but mature, normal glial tissue with immunoreactivity for glial fibrillary acidic protein. The patient had no previous history of head trauma or surgery, and no evidence of central nervous system connection was noted on the radiological or operative findings. This mass was regarded as a primary glial heterotopia rather than an acquired encephalocele.

Original Articles

Minocycline Attenuates the Development of Allodynia: An Immunohistochemical Study on CD11b, GFAP and c-Fos in the Spinal Dorsal Horn in SD Rat.: Gu Kang, Ki Young Choi, Min Sup Lee, Young Jun Ahn, Seong Sik Kang, Il Young Cheong, Wanjoo Chun, Sung Soo Kim; Korean J Pathol. 2004;38(5):311-318.

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Abstract PDF: BACKGROUND
Minocycline, a semisynthetic second-generation tetracycline, is an antibiotic that has excellent ability to penetration into the CNS via the brain-blood barrier. Minocycline has emerged as a potent inhibitor of microglial activation, and it is an effective neuroprotective agent in experimental brain ischemia. Glial cell activation and proliferation are known to be associated with neuropathic pain in the peripheral nerve injuries.
METHODS
The fifty percent threshold of withdrawal responses was measured in the hindpaws of SD rats following tight ligation of left fifth lumbar spinal nerve. Rats were sacrificed at 1, 3, 5, and 7 days and at 0.5, 1, 2, and 4 h post ligation (n=5/group/time point). Immunohistochemistry for GFAP, CD11b and c-Fos was done on the spinal cord at the level of the fifth lumbar nerve. Minocycline (45 mg/kg) and normal saline (300-400 microL) were administered intraperitoneally, 1 day and 1 h before the operations, and every day postoperatively until the rats were sacrificed.
RESULTS
Treatment with minocycline reduced allodynia and the expressions of CD11b at 5 days and c-Fos at 1 and 2 h post operation compared with the saline treatment (control). CONCLUSIONS: It was thought that minocycline reduced the allodynia induced by tight ligation of the fifth lumbar spinal nerve in rats through the inhibition of microglial activation and c-Fos expression.

Effect of Antenatal Dexamethasone Treatment on Neuronal Morphogenesis.: Soo Jeong Yoon, Heasoo Koo, Chong Il Kim; Korean J Pathol. 2005;39(2):81-90.

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Abstract PDF: BACKGROUND
Glucocorticoids (GCs) are essential for normal development and the maturation of the central nervous system. The aim of this study was to determine the effects of antenatal dexamethasone (DEXA) treatment on neuronal morphogenesis and on the glial cell line-derived neurotrophic factor (GDNF) protein expression in neonatal rat.
METHODS
Pregnant Sprague-Dawley rats were injected with saline (the control), or 0.2 mg/kg/day DEXA or 0.8 mg/kg/day DEXA at 17th, 18th and 19th day of gestation. The newborn rat brains were examined at postnatal days 1 (n=75) and 10 (n=78).
RESULTS
The DEXA-treated groups showed distorted architectures of neurons in the cerebral cortex, hippocampus and cerebellar cortex at postnatal days 1 and 10 with an increased number of proliferating cell nuclear antigen (PCNA)-positive cells. The cerebellar cortex in the DEXA-treated groups showed delayed development with more PCNA-positive cells in the internal granular cell layer. The Purkinje cells showed a markedly decreased number and the decreased length of the dendritic processes. The GDNF positive reaction was decreased in the DEXA-treated groups in a dose-dependent manner.
CONCLUSIONS
The developmental changes and neuronal degeneration at postnatal days 1 and 10 in the newborn rats that were exposed to DEXA at the late gestational age were associated with increased proliferative activity and a decreased level of GDNF protein expression.

Cytokine Expression on Microglial Proliferation and Apoptosis in Rat Lumbar Spinal Cord Following Unilateral Sciatic Nerve Transection.: Sang Pyo Kim, Seung Il Suh, Young Rok Cho, Seung Che Cho, Seung Pil Kim, Jong Wook Park, Jyung Sik Kwak; Korean J Pathol. 1998;32(2):94-103.

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Abstract PDF: This study was carried out to elucidate the cytokine mRNAs expression and morphological features according to a microglial proliferation and apoptosis in a rat lumbar spinal cord, after a right sciatic nerve transection. The control group was composed of 5 rats (Spraque-Dawley) and the experimental group was composed of 70 rats. On post operation day (pod) 1, 2, 3, 5, and 7 eight rats were sacrificed on those days. On pod 10 five rats were sacrificed as well as five rats sacrificed on post operation weeks 2, 3, 4, 5, and 6. On light microscopy, activated microglia were often found in a perineuronal position around motoneurons in the ventral gray matter and more randomly distributed throughout the neuropil in the dorsal gray matter of lumbar spinal cord. GSA I-B4-positive microglia began to increase from 1 day after transection, and reached peak at 2~3 days and it persisted at 5~7 days and decreased thereafter. TUNEL-positive microglia was not observed in control group and began to increase from 5 days after transection and increased gradually until 3 weeks and decreased thereafter. On in situ RT-PCR, the positive signal for IL-1alpha and IL-6 mRNA was found mainly in the cytoplasm of the activated microglia and astrocytes at 1 day after transection and showed stronger signal at 3 days and decreased gradually until 10 days. TNF-alpha mRNA was detected 1 day after transection and remained for 7 days and localized to activated microglia as well as probably some astrocytes. The signal intensity of IL-1alpha and IL-6 mRNA was generally stronger than TNF-alpha mRNA. On transmission electron microscopy, there were chromatin condensation with margination toward nuclear membrane and condensation of cytoplasm at 3 days after transection. Apoptotic bodies were found after 5 days and increased gradually until 3 weeks. According to the above findings, it is concluded that apoptosis appears to be one mechanism by which activated microglia are gradually eliminated and cytokine expression seems to played an active role in the microglial turnover.

Heterotopic Glial Nodule in the Lung of an Anencephaly Patient : An autopsy case.: Hye Joung Lee, Soo Min Kang, Gyung Hyuck Ko; Korean J Pathol. 1991;25(5):457-461.

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Abstract: The heterotopic and tissues may be divided into two categories: those that are found in the head and neck region, and those that arise elsewhere. The latter type is rare and most cases are found in the lungs of patients with neural tube defect, particularly anencephaly. Our report descrives anencephalic male infant with heterotopic glial nodules in both lungs. The largest nodule is 2x1.5x1 cm, locates in the lower lobe of the left lung, and has a round gray-white cut surface with cystic spaces. Microscopically, the nodules consist of irregularly arranged astrocytes and glial fibers, in which are embedded gland-like or cystically dilated bronchioles. The astrocytes and glial fibers are strongly positive for glial fibrillary acidic protein and show astrocytic filaments on electron microscopy. This will be an additional case supporting the amniotic fluid aspiration/implantation theory of pathogenetic mechanism of distal heerotopic glial tissue.

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