Biomedical subjects

Mitsuhiro Hasegawa

Publications and source records attributed to Mitsuhiro Hasegawa.

At least 19 recordsLinked to original sources

PubMed2006

Cerebellar gliofibroma with numerous psammoma bodies.

A case of psammoma body rich gliofibroma is reported. Computed tomography (CT) showed a high-density mass without contrast enhancement in the right cerebellar hemisphere. Magnetic resonance images (MRI) demonstrated a mass with a mixture of high- and iso-intensity regions without meningeal attachment on both T1- and T2-weighted images. Pathological examinations revealed a biphasic pattern consisting of tumor cells in sparce cellularity and dense fibrous connective tissue. Numerous psammoma bodies of uniform size were found in the stroma. The tumor cells expressed glial fibrillary acidic protein and S-100, but not p53, vimentin and EMA. This is the first report describing a case of psammomatous gliofibroma.

Adult↗

PubMed2006

Absence of tight junctions between microvascular endothelial cells in human cerebellar hemangioblastomas.

OBJECTIVE: Endothelial tight junctions form the main barrier of the blood-brain barrier (BBB). In human hemangioblastomas, cyst formation is a common and important clinical manifestation. Although most researchers consider that the cyst formation in hemangioblastomas may be caused by the breakdown of the BBB, the underlying molecular mechanisms for cyst formation remain unknown. At present, there are few reports about the change of tight junctions in microvessel endothelium of human hemangioblastomas. The purpose of this research is to investigate the change of tight junction and its major molecular components in microvessel endothelium of human hemangioblastomas. METHODS: Twenty-four consecutive patients with cerebellar hemangioblastomas were studied. Tight junctions in the microvessels of hemangioblastomas and the control brain were examined by electron microscopy. Immunohistochemistry and double immunofluorescent microscopy were used to analyze the expression of CLN5 and its relationship with astrocytic endfeet in the control brain and hemangioblastomas. Quantitative real-time reverse-transcriptase polymerase chain reaction and Western blots were used to investigate the expression level of CLN5 in hemangioblastomas. Triple immunofluorescent microscopy was used to analyze the coexpression of vascular endothelial growth factor, vascular endothelial growth factor-R1, and placenta growth factor on microvessels of hemangioblastomas. Clinical and experimental data were correlated and analyzed by the one-way analysis of variance, Kruskal-Wallis test, and Spearman rank correlation test. RESULTS: In the control brain, the paracellular cleft between adjacent endothelial cells is sealed by continuous strands of tight junctions. In cystic hemangioblastomas, a significant paracellular cleft could be found between adjacent endothelial cells. Some endothelial cells were connected with adherens junction and no tight junction was found between them. Compared with the control brain, expression of CLN5 was decreased in cystic hemangioblastomas (P < 0.05). Phosphorylated CLN5 was detected in most hemangioblastomas, but not in the control brain. Microvessels in hemangioblastomas showed a significant absence of astrocytic endfeet. Coexpression of vascular endothelial growth factor, vascular endothelial growth factor-R1, and placenta growth factor was detected in the endothelial cells. The Spearman rank correlation test showed a significant correlation between a greater degree of CLN5 expression and less morphological cystic formation in these patients studied (correlation coefficient = -0.520; P = 0.009). CONCLUSION: The continuity of tight junctions of the BBB is interrupted in human cerebellar hemangioblastomas. Significant absence of astrocytic endfeet and tight junctions can be found in microvessels of hemangioblastomas, which may lead to the breakdown of the BBB in these tumors. These findings suggest that the absence of tight junctions might play a role in cyst formation of hemangioblastomas.

Adult↗

PubMed2006

C-kit gene mutation: common and widely distributed in intracranial germinomas.

OBJECT: Of the intracranial germ cell tumors (IGCTs), 10% of germinomas and most nongerminomatous tumors remain refractory to multimodality therapy. The authors investigated the mutation of c-kit and the expression of its product KIT in IGCTs to identify tumors susceptible to imatinib mesylate, a synthetic agent targeting KIT. METHODS: The authors investigated 26 IGCTs, including 13 germinomas, five mixed germ cell tumors (MGCTs), four immature teratomas (ITs), and two each of yolk sac tumors and choriocarcinomas. These tumors were examined for the expression of KIT and CD34 by immunohistochemical analysis, and for mutations in exons 2, 8 to 11, 13, and 17 of c-kit. Strong KIT expression was found in the cell membrane of germinomas (100%) and germinomatous cells of MGCTs (80%), as well as in the cytoplasm of epithelial and smooth-muscle cells of ITs. The membranous expression of CD34 was found in the nongerminomatous tumor cells and the chondrocytes of MGCTs (60%), ITs (100%), and a choriocarcinoma (50%), but not in germinomas and germinomatous cells. A total of five missense mutations distributed in exons 2, 11, 13, and 17 of c-kit were detected in three (23%) of the 13 germinomas. The novel mutations E73K, T96M (both in exon 2), and A636V (in exon 13) were detected in a single tumor. The presence or type of c-kit mutation was not correlated with patient prognosis. CONCLUSIONS: Immunohistochemical analysis of KIT expression is useful for the diagnosis of germinoma. This study may help in clarifying the pathogenesis of IGCTs and in identifying tumors susceptible to drugs targeting KIT.

Adolescent↗

PubMed2006

[A case of atretic cephalocele].

We report a case of atreric cephalocele. A 13-year-old boy who was developmentally normal was admitted to our hospital, complaining of scalp mass located at the midparietal region. He was noticed to have had it since his birth. Physical examination revealed 2.5 x 2.5cm, round, skin-covered midline subscalp mass with a hairless top. Bone 3D-CT showed bone defect at the base of the mass. MRI and MR venography showed the embryonic positioning of the straight sinus. He was treated with surgical excision of the mass, and fibrous tract extending intracranially at the base of the lesion was identified. Pathologic examination showed it to be meningocele.

Adolescent↗

PubMed2005

Oxidized galectin-1 advances the functional recovery after peripheral nerve injury.

Oxidized galectin-1 has been shown to promote axonal regeneration from transected-nerve sites in an in vitro dorsal root ganglion (DRG) explant model as well as in in vivo peripheral nerve axotomy models. The present study provides evidence that oxidized galectin-1 advances the restoration of nerve function after peripheral nerve injury. The sciatic nerve of adult rats was transected and the distal nerve was frozen after being sutured into a proximal site with four epineurial stitches. An osmotic pump delivered oxidized galectin-1 peripherally to the surgical site. Functional recovery was assessed by measurement of the degree of toe spread of the hind paw for 3 months after the sciatic nerve lesion. The recovery curves of toe spread in the test group showed a statistically significant improvement of functional recovery after day 21 by the application of oxidized recombinant human galectin-1 (rhGAL-1/Ox) compared to the control group. This functional recovery was supported by histological analysis performed by light microscopic examination. The regenerating myelinated fibers at the site 21 mm distal to the nerve-transected site were quantitatively examined at 100 days after the operation. The frequency distribution of myelinated fiber diameters showed that exogenous rhGAL-1/Ox increased the number and diameter of regenerating myelinated fibers; the number of medium-sized (6-11 microm in diameter) fibers increased significantly (P<0.05). These results indicate that oxidized galectin-1 promotes the restoration of nerve function after peripheral nerve injury. Thus, rhGAL-1/Ox may be a factor for functional restoration of injured peripheral nerves.

Animals↗

PubMed2005

Cyclin D1 is overexpressed in atypical teratoid/rhabdoid tumor with hSNF5/INI1 gene inactivation.

OBJECT: Although atypical teratoid/rhabdoid tumor (AT/RT) is known to generate through inactivation of the hSNF5/INI1 gene on chromosome 22q, the downstream molecular mechanism remains unclear. We histologically and molecularly reviewed our pediatric brain tumors for unrecognized AT/RTs and evaluated the role of cyclin D1, a potential molecular target of hSNF5/INI1. METHODS: We analyzed 16 tumors under three years of age: seven medulloblastomas, three anaplastic ependymomas (E IIIs), two each of supratentorial primitive neuroectodermal tumors (sPNETs) and choroid plexus carcinomas (CPCs), and one each of neuroblastoma and pineoblastoma. Immunohistochemistry for glial fibrillary acidic protein, vimentin, epithelial membrane antigen, smooth muscle actin and cyclin D1 was performed. Polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis with direct sequencing, differential PCR and microsatellite analysis were conducted for hSNF5/INI1mutation, homozygous deletion and loss of heterozygosity (LOH) on 22q, respectively. Because of the presence of rhabdoid cells and the polyimmunophenotypic features, the diagnosis was revised to AT/RT in five (31%) tumors, namely, two E IIIs and one each of medulloblastoma, CPC and pineoblastoma. Three of them harbored such hSNF5/INI1 aberrations as germline single base deletion (492/6 delC) and missense mutation (C157T) together with LOH 22q or homozygous deletion. Cyclin D1 was overexpressed in those three tumors but not in the two that lacked hSNF5/INI1 inactivation. CONCLUSION: AT/RT can be misdiagnosed as a variety of tumors, including ependymoma that potentially harbors LOH 22q. Our data indicate that cyclin D1 is a target of hSNF5/INI1in primary tumors.

Central Nervous System Neoplasms↗

PubMed2005

CT arteriography for orbital tumors: diagnostic and surgical value.

The aim of this study is to investigate the efficacy of dynamic computed tomography (CT) during selective angiography (CT-arteriography) of orbital tumors in the evaluation of intratumoral vascular anatomy, feeding artery territory, and histological diagnosis. Among 35 consecutive cases with various orbital lesions, those cases showing tumor staining or pooling of the contrast medium on digital subtraction angiography (DSA) were evaluated by CT-arteriography (n = 14). The information obtained by CT-arteriography was compared with that provided by enhanced MRI (n = 31) and dynamic MRI (n = 21), in which the contrast medium was injected intravenously. In addition to the visualization of fine vascular anatomy, CT-arteriography emphasized areas of nodular enhancement and non-enhancing cystic/necrotic components as well as the intratumoral feeding arteries. Patterns of CT-arteriography were categorized into three subgroups: homogeneous enhancement (benign lymphoid lesion), partial enhancement (schwannomas and carcinomas), and patchy multinodular enhancement (specific for cavernous angiomas). In addition, CT-arteriography with selective arterial catheterization clearly delineated the feeding artery territories. CT-arteriography, with a minimal dose of contrast medium, can offer significant advantages over intravenously injected dynamic neuroimaging, and provides additional valuable preoperative information about the orbital tumor under investigation.

Adult↗

PubMed2005

Oxidized galectin-1 is an essential factor for peripheral nerve regeneration.

Although many factors have been implicated in the regenerative response of peripheral axons to nerve injury, the signals that prompt neurons to extend processes in peripheral nerves after axotomy are not well-understood. As shown in the first chapter, oxidized recombinant human galectin-1 (rhGAL-1/Ox), which lacks lectin activity, promotes initial axonal growth in an in vitro peripheral nerve regeneration model at low concentrations (pg/ml). At a similarly low concentration, rhGAL-1/Ox has also been shown to be effective in enhancing axonal regeneration using in vivo experiments. Moreover, the application of functional anti-rhGAL-1 antibody strongly inhibited axonal regeneration in vivo as well as in vitro. Since galectin-1 (GAL-1) is expressed in the regenerating sciatic nerves as well as in both sensory and motoneurons, these results indicate that GAL-1, which is secreted into the extracellular space, is subsequently oxidized and then may regulate initial repair after axotomy. This possibility was confirmed by Western blot analysis, which revealed that both reduced and oxidized forms of GAL-1 are present in culture media of DRG neurons and immortalized adult mouse Schwann cells (IMS32). Externalized GAL-1/Ox has been found to stimulate macrophages to secrete an axonal regeneration-promoting factor. From these results, we propose that axonal regeneration occurs in axotomized peripheral nerves as a result of cytosolic reduced GAL-1 being released from Schwann cells and injured axons, which then becomes oxidized in the extracellular space. GAL-1/Ox in the extracellular space stimulates macrophages to secrete a factor that promotes axonal growth and Schwann cell migration, thus enhancing peripheral nerve regeneration and functional recovery. These results suggest that rhGAL-1/Ox may be a novel factor for functional restoration of injured peripheral nerves.

Animals↗

PubMed2005

Correlation of gamma-catenin expression with good prognosis in medulloblastomas.

OBJECT: Medulloblastoma is a malignant cerebellar tumor of childhood and is difficult to cure due to frequent cerebrospinal fluid dissemination. Amplification of the c-myc gene (4%) and messenger (mRNA) overexpression (50%) are known to be adverse prognostic indicators. Because mRNA overexpression cannot be explained by gene amplification alone, mechanisms other than gene amplification are postulated. Molecules on the Wnt signal pathway in primary tumors were examined. METHODS: Immunohistochemical and cytogenetic examinations of beta- and gamma-catenin, c-myc, N-myc, and cyclin D1 in 24 primary medulloblastomas were conducted, and their clinical relevance was evaluated. Cytoplasmic/membranous staining of beta- and gamma-catenin was detected in 19 (79%) and nine (37%) cases, respectively, and nuclear expression of cyclin D1 and c-myc was detected in six (25%) and 21 (83%) cases, respectively. The expression levels of gamma-catenin in Western blot analysis and immunohistochemistry were similar. By differential polymerase chain reaction, c-myc and N-myc were amplified separately in two large cell/anaplastic medulloblastomas. No cyclin D1 amplification, or beta- or gamma-catenin mutations were found. Kaplan-Meier analysis revealed no dissemination at diagnosis (Chang Grade M0) and gamma-catenin expression was correlated with good prognosis (p = 0.0002 and 0.003, respectively). Expression of gamma-catenin was also significant in the M0 group (p = 0.022). Expression of cyclin D1 showed a trend toward adverse outcome (p = 0.057) and all patients in whom cyclin D1 expression was found died of disease. CONCLUSIONS: Expression of gamma-catenin is of great prognostic value and its immunohistochemistry may be useful for further stratification of treatment. Cyclin D expression may have the potential to be an adverse prognostic indicator.

Adolescent↗

PubMed2004

Frequent gene amplification and overexpression of decoy receptor 3 in glioblastoma.

The decoy receptor 3 (DcR3) gene is amplified at high frequency in human lung, colon, and liver cancers. DcR3 has been demonstrated to produce a secreted member of the tumor necrosis factor receptor superfamily that negatively regulates Fas-mediated apoptosis. In this study we examined DcR3 gene amplification, DcR3 mRNA expression, and DcR3 protein expression in 46 human astrocytic brain tumors by quantitative genomic PCR, quantitative reverse transcription-PCR, and immunohistochemistry, respectively. The DcR3 gene amplification was detected in none of 6 (0%) low-grade astrocytomas, 1 of 16 (6%) anaplastic astrocytomas, and 6 of 24 ( 25%) glioblastomas. Six of 7 (86%) cases with gene amplification exhibited both mRNA overexpression and/or protein overexpression, suggesting that DcR3 mRNA and protein were expressed more abundantly in the cases with gene amplification. We thus concluded that high DcR3 mRNA expression and protein expression may be positively related to the gene amplification in astrocytic brain tumors, especially glioblastomas. Further, we speculated that the DcR3 gene amplification with overexpression may be responsible for malignant features in glioblastomas.

Adolescent↗

PubMed2004

Obstructive hydrocephalus associated with arachnoid cyst in the elderly.

We present a case of a symptomatic frontal arachnoid cyst associated with hydrocephalus in an elderly patient. It is well known that symptomatic arachnoid cysts usually develop at an early age. This condition is rarely observed in the elderly. The authors hypothesized that compression of the brain and obstructive hydrocephalus caused the arachnoid cyst to become symptomatic.

Aged↗

PubMed2004

Autologous amnion graft for repair of myelomeningocele: technical note and clinical implication.

OBJECTIVE AND IMPORTANCE: Amniotic membrane can be used as autologous reconstruction graft material when aseptically obtained. We introduce here a novel repair technique using autologous amnion graft, and report a case presentation of myelomeningocele successfully treated with this graft material. TECHNIQUE: Amniotic membrane, which was composed of amnion and chorion, was aseptically harvested at cesarean section. Removing chorionic tissue, amnion containing monolayer of amniotic epithelial cells and underlining fibrous tissue was isolated. After the procedure of reconstruction of neural and meningeal elements, the membrane was placed as onlay autograft over the reconstructed neural structure followed by suture of undermined skin flap without any myocutaneous flap transfer technique or fascial transposition from paraspinal muscles. RESULTS: The postoperative healing process of the wound was excellent. CONCLUSION: Autograft of amniotic tissue has no risks of rejection, foreign body reaction, or transmission of slow virus infection to reconstruct the lesion of newborn patient. Amnion autograft would be a biologic rationale to promote wound healing, being applied as a part of a variety of pediatric neurosurgical procedure.

Adult↗

PubMed2004

Subfrontal schwannoma without hyposmia--case report.

A 44-year-old man presented with a rare subfrontal schwannoma with headache. He had undergone radiation therapy for a pineal lesion 30 years previously, but the histology was not verified. On admission, neurological examination revealed no focal deficits including hyposmia. Computed tomography demonstrated a mass measuring 5 x 3 cm in the right anterior cranial fossa. Magnetic resonance imaging revealed a heterogeneously enhanced mass with multiple cysts. The tumor, which was clearly separable from the surrounding normal brain, was totally resected through a right frontal craniotomy. There was no adhesion between the tumor and the olfactory groove or cribriform plate. The frontal base dura was suspected to be the tumor attachment. The patient was discharged without hyposmia. Histological examination revealed a typical pattern of schwannoma consisting of Antoni type A and type B. Immunohistochemical staining was positive for S-100 protein but negative for epithelial membrane antigen. Subfrontal schwannoma not associated with the olfactory groove or cribriform plate is extremely rare. The operative findings and absence of hyposmia suggest that the meningeal branch of the trigeminal nerve was the origin of the tumor. However, the possibility of radiation-induced reactive Schwann cells cannot be excluded.

Adult↗

PubMed2004

Recurrent intracranial solitary fibrous tumor with cerebrospinal fluid dissemination. Case report.

Solitary fibrous tumor (SFT) is a benign and rare neoplasm. To date, only 37 patients with intracranial SFTs have been reported. Although a number of the tumors were recurrent and some later underwent malignant transformation, none of these lesions progressed to cerebrospinal fluid (CSF) dissemination. In this paper the authors report a case of SFT in which the lesion recurred several times and ultimately was disseminated by the CSF. The patient was a 63-year-old woman with multiple intracranial and spinal tumors. Fifteen years before this presentation, at the age of 48 she had been hospitalized for resection of a falcotentorial tumor. During the ensuing 15 years she underwent multiple surgeries and sessions of radiation therapy for recurrent lesions. The exclusive location of her tumors in the subarachnoid space at the end of this 15-year period indicate CSF dissemination of the tumor. The tumor that was resected when the patient was 48 years old and the latest resected lesion were analyzed by performing immunohistological CD34, epithelial membrane antigen, vimentin, S100 protein, and reticulin staining, and determining the MIB-1 labeling index (LI). Most of the results were identical, and both tumors were diagnosed as SFT according to a staining pattern that showed a strong and diffuse positive reaction for CD34. Nevertheless, the authors noted that the MIB-1 LI increased from less than 1% in the original tumor to 13% in the latest tumor. The increased proliferation of MIB-1 indicates that the malignant transformation could have occurred during tumor recurrence with CSF dissemination.

Antigens, CD34↗

PubMed2004

Successful treatment of hemifacial spasm with selective facial nerve block using doxorubicin (adriamycin) under local anesthesia.

OBJECTIVE: To describe our experience with selective chemical rhizotomy of facial nerves using adriamycin (ADM) in a patient with hemifacial spasm (HFS). This unique technique is less invasive than intracranial neurosurgery and enables one to perform a permanent nerve block under local anesthesia. PATIENT: The patient, a 73-year-old female, had difficulty opening her left eye. Following unsuccessful treatment with anti-epileptic medicine, she received selective intraneural injections of ADM under local anesthesia. One week after the surgery the spasms had disappeared completely. No major complications were caused by this procedure and there had been no recurrence of spasms 3 years after the surgery. RESULTS: It is thought that recurrence of HFS should be observed after simple neurotomy due to regrowth of nerve fibers. However, this did not occur after chemical rhizotomy with ADM. This method clearly differs from previously used varieties of simple neurotomy because the latter technique does not cause severe destructive changes in the facial motor nucleus. CONCLUSION: Selective facial nerve chemical rhizotomy with ADM under local anesthesia may be effective in treating a subgroup of patients with HFS, especially elderly patients and those in the high-risk group for general anesthesia and intracranial neurosurgery.

Aged↗

PubMed2003

Meningioma associated with intraosseous lipoma.

Intraosseous lipomas of the skull are quite rare and only eight cases have been reported. The lipoma in our case was different from that in others in that it showed remarkable proliferation of collagen tissue. This is the first report of meningioma occurring after removal of an intraosseous lipoma of the skull. This report concerns a rare case of a 32-year-old female who developed a huge convexity meningioma 11 years after successful removal of intraosseous lipoma of the left frontoparietal bone. The meningioma originated from the convexity where the lipoma had been, and extended intracranially to the sphenoid ridge. The patient underwent surgical exploration showing that the meningioma had invaded the frontoparietal convexity bone and was firmly attached to the coronal suture with a large dural defect. This rare coincidence suggests that proliferative changes of the intraosseous lipoma and meningeal neoplasm may be the result of the same, as yet unknown, mechanism.

Adult↗

PubMed2003

Oxidized galectin-1 stimulates the migration of Schwann cells from both proximal and distal stumps of transected nerves and promotes axonal regeneration after peripheral nerve injury.

Oxidized galectin-1 has recently been identified as a key factor that plays important roles in initial axonal growth in injured peripheral nerves. The aim of this study was to investigate the effects of oxidized galectin-1 on regeneration of rat spinal nerves using acellular autografts (containing no viable cells) and allografts (containing no cell membranes) with special attention to the relationship between axonal regeneration and Schwann cell migration. Immunohistochemically, endogenous galectin-1 was expressed in dorsal root ganglion (DRG) neurons, spinal cord motoneurons, and axons and Schwann cells in normal sciatic nerves. Administration of oxidized recombinant human galectin-1 (rh-gal-lox, 5 ng/ml) in autograft model promoted axonal regeneration from motoneurons as well as from DRG neurons; this was confirmed by a fluorogold tracer study (p < 0.05). Anti-rh-gal-1 antibody (30 microg/ml) strongly inhibited axonal regrowth (p < 0.05). Pretreatment of allografts with rh-gal-lox stimulated the migration of Schwann cells not only from proximal stumps but also from distal stumps into the grafts, resulting in accelerated axonal regeneration (p < 0.05). Moreover, Schwann cell migration preceded the axonal growth in the presence of exogenous rh-gal-lox in the grafts. These results strongly suggest that local administration of exogenous rh-gal-lox promotes the migration of Schwann cells followed by axonal regeneration from both motor and sensory neurons, resulting in acceleration of neuronal repair. This technique may also be of value in the repair of human nerves.

Animals↗

PubMed2003

Frequent LOH at chromosome 12q22-23 and Apaf-1 inactivation in glioblastoma.

Glioblastoma (GB) often has loss of heterozygosity on the chromosomes, 1p, 10p, 10q, 11p, 17p, 19q, 22q, and several others. In the case of chromosome 12q, however, it remains to be seen whether LOH occurs. Apaf-1, the apoptotic protease activating factor-1, located at chromosome 12q22-23, is a major effecter of the p53 mediated apoptosis pathway, and Apaf-1 inactivation due to chromosome 12q22-23 LOH and hypermethylation may be involved in some of the neoplasms in malignancy. However, little is known about the frequency of the 12q22-23 LOH or the state of Apaf-1 in GB. To elucidate their involvement in GB, we analyzed a series of 33 GBs for chromosome 12q22-23 LOH, Apaf-1 mRNA expression, and Apaf-1 protein expression, using microsatellite analysis, reverse transcription (RT)-PCR analysis, and immunohistochemical (IHC) analysis, respectively. We also evaluated if and how the 12q22-23 LOH correlated with the p53 gene mutation and EGFR gene amplification. Chromosome 12q22-23 LOH was detected in 14 (42%) of 33 cases. Among the examined cases with LOH at 12q22-23, a low expression of Apaf-1 mRNA was detected in 9 (69%) of 13 cases, and a low expression of Apaf-1 protein was detected in 12 (86%) of 14 cases. The 12q22-23 LOH was significantly correlated with low expression of mRNA and protein (p<0.05, p<0.001 respectively). The p53 gene mutation and EGFR gene amplification were found in 13 cases (39%) and 8 cases (24%), respectively, and these gene alterations were inversely correlated. However, 12q22-23 LOH had no correlations with the p53 gene mutation or EGFR gene amplification. Six of 9 GBs (67%) with neither p53 gene mutation nor EGFR gene amplification tested positive for 12q22-23 LOH. These GBs are likely to belong to another subset independent from the 2 common genetic subsets in GB (one with p53 gene mutation and without EGFR gene amplification, and the other with EGFR gene amplification and without p53 gene mutation). Twenty-three (70%) out of the 33 GBs with the 12q22-23 LOH also tested positive for Apaf-1 inactivation or p53 gene mutation. This high frequency of alterations in the apoptosis-associated factors prompts a speculation that abrogation of the Apaf-1 and p53 mediated apoptosis pathway may play an important role in the tumorigenesis of GB.

Adult↗