Biomedical subjects

Masashi Fukayama

Publications and source records attributed to Masashi Fukayama.

At least 19 recordsLinked to original sources

PubMed2007

p73 gene promoter methylation in Epstein-Barr virus-associated gastric carcinoma.

To clarify the significance of p73 in Epstein-Barr virus (EBV)-associated gastric carcinoma (GC), the immunohistochemical expression and CpG-island methylation of p73 were evaluated in cancer tissues and adjacent nonneoplastic tissues of GC with and without EBV infection. Loss of p73 expression by immunohistochemistry was specific to EBV-associated GC (11/13) compared to EBV-negative GC (3/38), which was independent of abnormal p53 expression. With methylation-specific polymerase chain reaction (MSP), the aberrant methylation of p73 exon 1 was similarly specific to EBV-associated GC (12/13), and also rare in EBV-negative GC (2/38). Bisulfite sequencing for p73 exon 1 and its 5' region confirmed the MSP results, showing uniform and high-density methylation in EBV-associated GC. Comparative MSP analysis of p14, p16 and p73 methylation, using 20 cases each of formalin-fixed and paraffin-embedded tissues of early GC with and without EBV infection, confirmed 2 types of methylation: global methylation with increased rates (p14 and p16) and specific methylation of p73 in EBV-associated GC. In nonneoplastic mucosa, p14, p16 and p73 methylation occurred in both EBV-associated (8/33, 6/34 and 3/38, respectively) and EBV-negative GC (6/23, 4/35, and 1/35). p73 methylation was observed in the mucosa without H. pylori infection in all 4 samples. Loss of p73 expression through aberrant methylation of the p73 promoter occurs specifically in EBV-associated GC, together with the global methylation of p14 and p16. A specific type of gastritis, prone to a higher grade of atrophy and p73 methylation, may facilitate the development of EBV-associated GC.

Base Sequence↗

PubMed2007

Early relapse of JAK2 V617F-positive chronic neutrophilic leukemia with central nervous system infiltration after unrelated bone marrow transplantation.

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder characterized by a proliferation mainly of mature neutrophils. The prognosis is generally poor and an optimal therapeutic strategy remains to be determined. Allogeneic hematopoietic stem cell transplantation (HSCT) is expected to be the only curative therapy so far. We report a 46-year-old male with progressive CNL who underwent bone marrow transplantation from an HLA-matched unrelated donor. After engraftment was achieved on day 35, relapse of CNL was confirmed on day 50. The progression of CNL was very rapid afterward and infiltration to the central nervous system was observed. The Janus Kinase 2 (JAK2) V617F homozygous mutation was detected from the peripheral blood or bone marrow samples throughout the clinical course. From comparison with reports of successful HSCT for CNL in the literature, it was inferred that HSCT should be performed in a stable status before progression. Furthermore, JAK2 V617F-positive CNL may contain an aggressive disease entity in contrast to previous reports. Accumulation of experiences is required to establish a definite role of HSCT in the treatment of CNL and a prognostic significance of JAK2 mutation in CNL.

Antineoplastic Agents, Alkylating↗

PubMed2006

Accurate assessment of lymph vessel tumor emboli in invasive ductal carcinoma of the breast according to tumor areas, and their prognostic significance.

Lymph vessel tumor emboli (LVTEs) within tumors are difficult to distinguish from stroma-invasive tumor foci. The purpose of this study was to evaluate staining of LVTEs with hematoxylin-eosin (HE) and with D2-40 to determine whether LVTEs identified by HE staining alone are D2-40-positive LVTE and whether the presence of LVTE identified by HE or D2-40 staining is an accurate predictor of outcome in 151 patients with invasive ductal carcinoma (IDC) of the breast. We first attempted to identify LVTE in the stroma-invasive tumor area (intratumor area), the advance area, and the nontumor area by HE staining alone, and then LVTE identified by HE staining was confirmed by D2-40 staining. The number of LVTE identified by HE staining and D2-40 staining successively increased from the intratumor area to the nontumor area. Although D2-40 staining detected larger numbers of LVTE than HE staining in all tumor areas, the highest positive predictive value of LVTE was observed in the intratumor area, and the next was in the advance area, and then the nontumor area, and significant correlations were found between the numbers of LVTE stained by HE and D2-40 in the same tumor areas. LVTE identified by HE staining or D2-40 staining in the intratumor area or nontumor area significantly increased the risk for tumor recurrence or death of patients with IDC, independent of hormone receptor status or nodal status. The results of this study demonstrate that the existence of intratumoral LVTE and that the presence of intratumoral LVTE identified by HE staining or D2-40 staining are accurate predictors of the outcome of patients with IDC of the breast.

Adult↗

PubMed2006

Oncofetal protein glypican-3 in testicular germ-cell tumor.

The expression of an oncofetal protein, the glypican-3 (GPC3), was immunohistochemically evaluated in a wide variety of primary testicular germ-cell tumors (GCTs) in comparison with other markers, alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG)-beta, and OCT3/4. Eighty-nine cases of GCT including 22 cases of mixed GCT were evaluated with reference to each tumor component. GPC3 expression was observed in neoplastic cells of yolk-sac tumor (YST) (25/25), teratoma (2/10), components of syncytiotrophoblastic giant cells (STGCs) (10/14), and choriocarcinoma (1/3), but none in intratubular germ-cell neoplasias, unclassified type (0/33), seminomas (0/61), or embryonal carcinoma (0/19). All cases of YST showed diffuse labeling of neoplastic cells in cytoplasmic and membranous patterns, and the positive area of GPC3 was much larger than that of AFP. Glandular structures in teratomas showed GPC3 immunostaining as well as AFP. Although the number of GPC3-positive cells was smaller in STGC components and choriocarcinoma, there was no diffusion artifact in GPC3 immunostaining, as was frequently encountered in hCG-beta staining. Thus, GPC3 is a unique oncofetal protein, which is useful as an immunohistochemical marker for GCT differentiated to extraembryonic tissue, especially YST.

Antigens, Neoplasm↗

PubMed2006

Identification of ROBO1 as a novel hepatocellular carcinoma antigen and a potential therapeutic and diagnostic target.

PURPOSE: Hepatocellular carcinoma is the most common primary malignancy of the liver and accounts for as many as one million deaths annually worldwide. The present study was done to identify new transmembrane molecules for antibody therapy in hepatocellular carcinoma. EXPERIMENTAL DESIGN: Gene expression profiles of pooled total RNA from three tissues each of moderately differentiated and poorly differentiated hepatocellular carcinoma were compared with those of normal liver, noncancerous liver tissue in hepatocellular carcinoma patients, 30 normal tissue samples, and five fetal tissue samples. Target genes up-regulated specifically in hepatocellular carcinoma were validated by immunohistochemical analysis and complement-dependent cytotoxicity assay using monoclonal antibodies generated against target molecules. RESULTS: The human homologue of the Drosophila Roundabout gene, axon guidance receptor homologue 1, ROBO1/DUTT1, a member of the immunoglobulin superfamily, was highly expressed in hepatocellular carcinoma, whereas it showed only a limited distribution in normal tissues. On immunohistochemical analysis using a newly generated anti-ROBO1 monoclonal antibody, positive signals were observed in 83 of 98 cases of hepatocellular carcinoma (84.7%). The mAb B2318C induced complement-dependent cytotoxicity in ROBO1-expressing cell lines and in the liver cancer cell line PLC/PRF/5. Strikingly, the ectodomain of ROBO1 was detected not only in the culture medium of liver cancer cell lines (PLC/PRF/5, HepG2, etc.) but also in sera from hepatocellular carcinoma patients (6 of 11). CONCLUSIONS: This is the first report that ROBO1 is overexpressed in hepatocellular carcinoma and shed into serum in humans. These observations suggest that ROBO1 is a potential new serologic marker for hepatocellular carcinoma and may represent a new therapeutic target.

Animals↗

PubMed2006

Fusion between CIC and DUX4 up-regulates PEA3 family genes in Ewing-like sarcomas with t(4;19)(q35;q13) translocation.

Ewing's family tumors (EFTs) are highly malignant tumors arising from bone and soft tissues that exhibit EWS-FLI1 or variant EWS-ETS gene fusions in more than 85% of the cases. Here we show that CIC, a human homolog of Drosophila capicua which encodes a high mobility group box transcription factor, is fused to a double homeodomain gene DUX4 as a result of a recurrent chromosomal translocation t(4;19)(q35;q13). This translocation was seen in two cases of soft tissue sarcoma diagnosed as Ewing-like sarcoma. CIC-DUX4 exhibits a transforming potential for NIH 3T3 fibroblasts, and as a consequence of fusion with a C-terminal fragment of DUX4, CIC acquires an enhanced transcriptional activity, suggesting that expression of its downstream targets might be deregulated. Gene expression analysis identified the ETS family genes, ERM/ETV5 and ETV1, as potential targets for the gene product of CIC-DUX4. Indeed, CIC-DUX4 directly binds the ERM promoter by recognizing a novel target sequence and significantly up-regulates its expression. This study clarifies the function of CIC and its role in tumorigenesis, as well as the importance of the PEA3 subclass of ETS family proteins in the development of EFTs arising through mechanisms different from those involving EWS-ETS chimeras. Moreover, the study identifies the role of DUX4 that is closely linked to facioscapulohumeral muscular dystrophy in transcriptional regulation.

Adult↗

PubMed2006

CpG island methylation status in gastric carcinoma with and without infection of Epstein-Barr virus.

PURPOSE: EBV-associated gastric carcinoma shows global CpG island methylation of the promoter region of various cancer-related genes. To further clarify the significance of CpG island methylator phenotype (CIMP) status in gastric carcinoma, we investigated methylation profile and clinicopathologic features including overall survival in four subgroups defined by EBV infection and CIMP status: EBV-associated gastric carcinoma and EBV-negative/CIMP-high (H), EBV-intermediate (I), and EBV-negative (N) gastric carcinoma. EXPERIMENTAL DESIGN: Methylation-specific PCR was applied to 106 gastric carcinoma cases. CIMP-N, CIMP-I, and CIMP-H status was determined by the number (0, 1-3, and 4-5, respectively) of methylated marker genes (LOX, HRASLS, FLNc, HAND1, and TM), that were newly identified as highly methylated in gastric cancer cell lines. The methylation status of 10 other cancer-related genes (p14, p15, p16, p73, TIMP-3, E-cadherin, DAPK, GSTP1, hMLH1, and MGMT) was also evaluated. RESULTS: Nearly all (14 of 15) of EBV-associated gastric carcinoma exhibited CIMP-H, constituting a homogenous group (14%). EBV-negative gastric carcinoma consisted of CIMP-H (24%), CIMP-I (38%), and CIMP-N (24%). EBV-associated gastric carcinoma showed significantly higher frequencies of methylation of cancer-related genes (mean number +/- SD = 6.9 +/- 1.5) even if compared with EBV-negative/CIMP-H gastric carcinoma (3.5 +/- 1.8). Among EBV-negative gastric carcinoma subgroups, CIMP-H gastric carcinoma showed comparatively higher frequency of methylation than CIMP-I or CIMP-N, especially of p16 and hMLH1. CIMP-N gastric carcinoma predominantly consisted of advanced carcinoma with significantly higher frequency of lymph node metastasis. The prognosis of the patients of CIMP-N was significantly worse compared with other groups overall by univariate analysis (P = 0.0313). CONCLUSION: The methylation profile of five representative genes is useful to stratify gastric carcinomas into biologically different subgroups. EBV-associated gastric carcinoma showed global CpG island methylation, comprising a pathogenetically distinct subgroup in CIMP-H gastric carcinoma.

Adult↗

PubMed2006

Computer-assisted analysis of biopsy specimen microvessels predicts the outcome of esophageal cancers treated with chemoradiotherapy.

PURPOSE: A computer-assisted microvessel analysis system was developed to evaluate correlations between the architecture of biopsy specimen microvessels and the outcome for patients with esophageal cancer treated with chemoradiotherapy. EXPERIMENTAL DESIGN: Biopsy specimens from 51 patients with esophageal cancer (T(2-3), any N, M0) treated with chemoradiotherapy were immunostained with an anti-CD31 antibody and quantified using computerized image analysis. We evaluated the association of several microvessel factors with overall survival, including the ratio of total microvessel perimeter to total tumor area (TP/TA), the tumor hypoxic ratio, and the ratio of total microvessel number to total tumor area (TN/TA). Results from traditional manual microvessel density (MVD) hotspot count and computerized hotspot count were compared and the relation between hotspot MVD count and survival rate was evaluated. RESULTS: The median follow-up time was 32 months. Both univariate and multivariate analyses revealed that computer-counted hotspot MVD and TN/TA and TP/TA ratios correlated significantly with the outcome of chemoradiotherapy. Kaplan-Meier survival curves showed that patients with high computer-counted hotspot MVDs and high TN/TA and TP/TA ratios had better overall survival rate than patients with low MVDs or ratios (P = 0.025, 0.008, and 0.031, respectively). Combining computer-counted MVD or TN/TA ratio with TP/TA ratio proved more predictive than any single factor. Two researcher-counted hotspot MVDs had no significant relation with outcome. CONCLUSION: Computer-assisted tumor microvessel analysis is a powerful tool in predicting the outcome for patients with esophageal cancer treated with chemoradiotherapy because intraobserver and interobserver variability is minimized.

Adult↗

PubMed2006

Podoplanin is expressed in subsets of tumors of the central nervous system.

Immunohistochemical analyses with the monoclonal antibody D2-40 were performed to ascertain the expression of podoplanin (a.k.a. T1-alpha, gp36, or aggrus) in tumors of the central nervous system (CNS) and to determine the diagnostic utility of the antibody. The analyses were performed on 325 tumors of various histologic types. The chief finding was almost constant immunoreactivity in ependymal tumors (37/40, 92.5%), choroid plexus papillomas (8/8, 100%), and meningiomas (100/100, 100%). The reactivity was considered "tissue-specific," as the corresponding normal tissue of each tumor was also found to express podoplanin. In addition, expression, not committed to the lineages, was found in many other tumor types, including astrocytic tumors, medulloblastomas, and hemangioblastomas, with variable frequency and intensity. The way of expression was not fully understood, but the expression in astrocytic tumors seemed to be associated with pronounced fibrous properties or malignant phenotype, as was shown by high-frequent expression in pilocytic astrocytomas (12/12, 100%) and glioblastomas (29/35, 82.9%). The present study has shown that podoplanin is expressed in several types of CNS tumors with variable frequency and intensity. Given the widespread expression of podoplanin, the antibody D2-40 is of little use in diagnostic practice for CNS tumors.

Animals↗

PubMed2006

Phenotype analysis by MUC2, MUC5AC, MUC6, and CD10 expression in Epstein-Barr virus-associated gastric carcinoma.

BACKGROUND: Gastric marker mucins (MUC5AC and MUC6) and intestinal marker molecules (MUC2 and CD10) have been used to determine the cell lineage of epithelial cell of gastric carcinoma (GC). METHODS: To clarify the characteristics of Epstein-Barr virus (EBV)-associated GC, 18 cases were immunohistochemically evaluated along with 56 cases of EBV-negative GC. RESULTS: MUC2 expression was lower in EBV-associated GC: immunostaining grades 0, 1, 2, 3, and 4 were observed in 10, 6, 1, 1, and 0 cases of EBV-associated GC, respectively, and in 18, 11, 15, 6, and 6 cases of EBV-negative GC, respectively (P = 0.013). CD10 positivity (grades 2-4) in EBV-associated GC was 6%, significantly lower than in EBV-negative GC (34%) (P = 0.030). When phenotypes of GC were categorized by the combined positivities of gastric markers (either MUC5AC or MUC6) and intestinal markers (either MUC2 or CD10), EBV-associated GC included primarily null (44%) and gastric (39%) types, but EBV-negative GC comprised null (7%), gastric (30%), intestinal (27%), and mixed (36%) types. The age of patients with gastric types was significantly younger for both EBV-associated GC and EBV-negative GC cases. CONCLUSIONS: Neoplastic epithelial cells of EBV-associated GC did not express MUC2 or CD10, and most of them were categorized as null or gastric types. EBV infection may occur in the epithelial cells of null or gastric phenotypes, which may be devoid of transdifferentiation potential toward intestinal phenotypes.

Aged↗

PubMed2006

Helicobacter pylori-negative / API2-MALT1 translocation-negative low-grade MALT lymphoma.

A 71-year-old man with a Helicobacter pylori infection-negative and API2-MALT1 translocation-negative extranodal marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type of the stomach has been followed conservatively for over 5 years. The lesion has shown no major morphological changes or malignant progression into a diffuse large-cell type during the time course. The absence of genetic translocation of API2-MALT1 was confirmed with fluorescence in situ hybridization (FISH). The prognosis of H. pylori-negative and API2-MALT1 translocation-negative low-grade MALT lymphoma is unknown, and a standard treatment for such lymphoma has yet to be defined. The case of MALT lymphoma negative for both of the above factors that we report has shown no obvious rapid progression or malignant change over the long-term course. Although curative operation and/or chemoradiotherapy should still be discussed as the treatment of choice, the treatment of this type of lymphoma must be carefully determined on a case-by-case basis, according to its biological status and prognosis.

Aged↗

PubMed2006

Prevalence of Epstein-Barr virus in Japan: trends and future prediction.

Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis and some malignancies including EBV-associated-lymphomas. A large portion of adults all over the world are infected with EBV. In children, however, there are geographic variations. Most of the children in Asia and in other developing countries are infected in their early life, before 1 year of age (>90% of 5-9-year-old children are infected), while the age of primary infection is delayed in Western countries (approx. 50% of 5-9-year-old children are infected). The purpose of the present paper was to investigate the recent time trend of the EBV seropositivity among 5-7-year-old children living in Tokyo and its neighboring prefectures. Indirect immunofluorescein study for IgG antibody to viral capsid antigen was performed on 442 archival sera. Before the early 1990s, >80% of 5-7-year-old children were found to be seropositive, while the positivity rate decreased to 59% (P < 0.001) for the years 1995-1999. These results also showed that the delay in the age of primary infection is continuing and that the rate is estimated to be <50% in 2006. This result suggests that the delay will affect the incidence of EBV-associated disorders in Japan.

Adolescent↗

PubMed2006

Phyllodes tumor of the prostate with exuberant glandular hyperplasia.

Reported herein is an unusual case of prostatic phyllodes tumor with exuberant glandular hyperplasia that led to misdiagnosis of adenocarcinoma. The tumor was detected in a 52-year-old man who had a 1 year history of dysuria. Adenocarcinoma of the prostate was diagnosed from a needle biopsy specimen. The patient received hormonal therapy for 6 months and underwent radical prostatectomy. Histologically, the tumor had an atypical stromal cell proliferation and elongated slit-like glands characteristic of a phyllodes tumor. The tumor was also accompanied by a florid proliferation of small acini, most of which lacked basal cells, a common manifestation of adenocarcinoma in the overall tumor area. The following features of the resected tumor were helpful for concluding that these acini were benign: lack of cytological anaplasia in spite of structural atypia, presence of scattered basal cells confirmed by immunohistochemistry (high-molecular-weight cytokeratin), and histological transition from these acini to apparently benign slit-like glands. The final diagnosis was then made as 'phyllodes tumor of the prostate with exuberant glandular hyperplasia'. Atypical stromal cells might provide a clue for the recognition of this rare tumor at initial diagnosis by needle biopsy.

Adenocarcinoma↗

PubMed2006

Epigenetic instability and chromosomal instability in hepatocellular carcinoma.

The aim of this study was to clarify the association between the epigenetic instability phenotype and the chromosomal instability phenotype in primary hepatocellular carcinoma (HCC). Sixty primary HCC tumors were examined. Methylation status for nine CpG islands (the p16, COX2, GSTP1, RASSF1A, E-cadherin, and APC gene promoters, and the MINT 1, 25, and 31 clones) was evaluated by methylation-specific polymerase chain reaction. Chromosomal structural alterations of these 60 HCC tumors were characterized in our previous study by using whole genomic array-based comparative genomic hybridization. We found that the epigenetic instability phenotype and the chromosomal instability phenotype are not mutually exclusive in hepatocarcinogenesis and that they do not show a simple cause-and-effect relationship. Hepatitis virus infection in the background liver was significantly associated with these instability phenotypes. Furthermore, we identified an epigenetic instability-dependent HCC that shows frequent epigenetic aberrations without chromosomal instability. It was noteworthy that epigenetic instability-positive and -negative HCCs displayed distinctive combinations of chromosomal structural alterations. In summary, by combined analyses of genetic and epigenetic aberration profiles in HCC, we obtained a comprehensive view of genomic alterations in hepatocarcinogenesis. Our results have clinical relevance because epigenetic instability-dependent HCCs may respond well to methylation inhibitory therapies.

Adult↗

PubMed2005

The use of a supercooling refrigerator improves the preservation of organ grafts.

Current medical transplantation confronts major problems such as the shortage of donors and geographical restrictions that inhibit efficient utilization of finite donor organs within their storage lives. To overcome these issues, expanding organ preservation time has become a major concern. We investigated whether a strategy which best preserves organ grafts can be achieved by the use of a newly developed refrigerating chamber, which is capable of establishing a supercooled and unfrozen state stably by generating an electrostatic field in its inside. When adult rat organs such as heart, liver, and kidneys were stored in the supercooled conditions, the levels of major biochemical markers leaked from the preserved organs were significantly lower than in the ordinary hypothermic storage. No apparent tissue damages were observed histologically after the supercooled preservation. Our results suggest that the use of this supercooling refrigerator improves organ preservation and may provide an innovative technique for human organ transplantation.

Animals↗

PubMed2005

Allelic dosage analysis with genotyping microarrays.

Genomic alternations, including dosage and allelic imbalance, constitute a major basis of neoplastic and other genetic disorders. Using oligonucleotide genotyping microarrays, here we report the development and usage of an algorithm, called genome imbalance map (GIM) algorithm, for allelic as well as total gene dosage analysis. Using the GIM algorithm, global genome imbalance status at over 100,000 loci was simultaneously analyzed with unprecedented accuracy and allelic discrimination.

Algorithms↗

PubMed2005

Genetic profile of hepatocellular carcinoma revealed by array-based comparative genomic hybridization: identification of genetic indicators to predict patient outcome.

BACKGROUND/AIMS: We conducted an analysis of chromosomal numerical aberrations and their clinical significance in hepatocellular carcinoma. METHODS: We analyzed 87 hepatocellular carcinomas by array-based comparative genomic hybridization with an array containing 800 bacterial artificial chromosome clones. RESULTS: Frequent (>30%) chromosomal losses on 1p36.1, 4q21-25, 4q34-35.1, 8p23.3b-11.1, 13q14.1-14.3, 16p13.3, 16q22.1-24.3b, 17p13.3-13.1 and 17p13.3-11, and gains on 1q21-44f, 2q21.2, 2q34, 3q11.2, 5p14.2, 5q13.2-14, 7p22, 7p14.2, 7q21.1, 7q22.3, 7q34, 8q12-24.3 and 17q23, were observed. Recurrent (>5%) amplifications were detected on 1q25, 8q11 and 11q11, and we discovered a novel homozygous deletion at 14q32.11. The extent of chromosomal aberrations correlated significantly with various clinicopathological characteristics of the tumors, and increased in a stepwise manner with the progression of hepatocellular carcinoma. We also identified novel chromosomal alterations that were significantly associated with a range of malignant phenotypes. Multivariate analysis revealed that both chromosomal loss on 17p13.3 and gain on 8q11 are independent prognostic indicators. CONCLUSIONS: Our results contribute to a complete description of genomic structural aberrations in relation to hepatocarcinogenesis and provide a valuable basis from which we can begin to understand the characteristics of tumors, predict patient outcomes and discover novel therapeutic targets for hepatocellular carcinoma.

Adult↗

PubMed2005

Secondary glioblastoma with advanced neuronal immunophenotype.

We describe an unusual progression of astrocytoma into secondary glioblastoma exhibiting advanced neuronal immunophenotype. A tumor of the left frontal lobe of a 35-year-old man was diagnosed as astrocytoma. The tumor was treated by partial removal with postoperative chemoradiotherapy, followed by extensive removal of the residual regrowing tumor 5 month later. A secondary tumor was discovered and partially resected 8 years later, but the patient died 11 months following the operation due to extensive tumor progression showing subarachnoidal and intraventricular dissemination. The secondary tumor was small cell-predominant, highly proliferative tumor with an extremely high MIB-1 labeling index (80%). Unexpectedly, most of the tumor cells were positive for neuronal markers (synaptophysin and NeuN), but not for glial fibrillary acidic protein (GFAP). Retrospective examination of the original tumor revealed not only diffuse GFAP expression, but also neuronal marker expressions in small numbers of tumor cells that were hard to discriminate from the other cells on hematoxylin-eosin (HE) stain. This way of malignant progression of astrocytoma was quite unusual. Although the secondary tumor was classified as glioblastoma according to World Health Organization (WHO) classification (2000), it might be categorized into new variants of malignant glioneuronal tumors proposed recently.

Adult↗