Papillary ependymoma is a rare variant of ependymoma and often gives rise to confusion with choroid plexus papilloma because of topographic, light microscopic and ultrastructural similarities. Here, we report two cases of papillary ependymomas regarding their unique clinicopathologic features and differential points from choroid plexus papilloma. Brain MRI revealed a large mass in the left lateral ventricle in one case and a 3cm sized mass in the pineal area and the 3rd ventricle in the other. Microscopically, the tumor was characterized by papillary and tubular structures. Immunohistochemically, the tumor cells in both cases expressed cytokeratins(CK22 and CAM 5.2) but did not express glial fibrillary acidic protein(GFAP), vimentin, epithelial membrane antigen, and S100 protein. This is a very unusual immunohistochemical feature for papillary ependymoma. Ultrastructurally, the tumor showed a mosaic pattern of tumor cells with frequent intercellular microrosettes having a few stubby microvilli, a few cilia and zonulae adherentes. The cytoplasmic processes were markedly reduced compared to conventional ependymoma. The cytoplasm did not contain intermediate filaments. Interestingly, the mitochondria showed abnormal features with a pleomorphic shape and abnormal cristae in both cases. These ultrastructural features enabled differentiation between papillary ependymoma and choroid plexus papilloma in addition to the light microscopic findings.
Adult ; Carcinoma, Papillary/*pathology/surgery ; Case Report ; Diagnosis, Differential ; Ependymoma/*pathology/surgery ; Fatal Outcome ; Female ; Follow-Up Studies ; Glioma/*pathology ; Human ; Magnetic Resonance Imaging ; Middle Age

OBJECTIVE: Vascular Endothelial Growth Factor (VEGF) is a potent stimulator of angiogenesis in solid tumors. Thrombospondin-1 (TSP-1) has inhibitory role in cancer cell proliferation and metastasis. To analyze the correlation with expression of VEGF and TSP-1 including microvessel density (MVD), the levels of VEGF/TSP-1 mRNA expression and microvessel count (MVC) were estimated in patients with invasive cervical carcinomas. METHODS: From 1996 to 1999, 37 carcinomas and 7 normal cervical tissues were collected, frozen and stored at -70 degrees C until used. The levels of VEGF and TSP-1 mRNAs were determined by quantitative RT-PCR. MVD was assessed by immunostaining for factor VIII-related antigen. The results are expressed as the largest number of microvessels present within a single x 40 field, and counted at x 100 field. RESULTS: Quantitative RT-PCR analysis demonstrated abnormally increased VEGF mRNA expression levels (>0.66) in 14 (37.8%) of 37 cervical carcinomas comparing to control groups (mean: 0.32+/-0.09) and abnormally low TSP-1 mRNA expression levels (<0.72) in 13 (35.1%) of 37 cervical carcinomas comparing to control groups (mean: 0.51+/-0.07). MVC was higher in tumors showing decreased expression of TSP-1 (but not statistically) (p<0.18) and overexpression of VEGF (p<0.05). When VEGF overexpression was accompanied with reduced TSP-1 expression, the microvessel density showed significantly increased pattern (p<0.05). CONCLUSION: Our study demonstrates that reduced expression of TSP-1 mRNAs and overexpression of VEGF mRNAs may be an important contributing factor in cervical carcinomas. Moreover, the inversed correlation of VEGF and TSP-1 mRNA expression can be an evidence of angiogenic role in cervical carcinomas.
Cell Proliferation ; Humans ; Microvessels* ; Neoplasm Metastasis ; RNA, Messenger* ; Thrombospondin 1 ; Uterine Cervical Neoplasms ; Vascular Endothelial Growth Factor A* ; von Willebrand Factor

PURPOSE: We used optical coherence tomography (OCT) for longitudinal evaluation of structural changes in the peripapillary retinal nerve fiber layer (RNFL), the macular ganglion cell-inner plexiform layer (GC-IPL), and the macula in patients with traumatic optic neuropathy. METHODS: From May 2012 to April 2015, the medical records of 20 patients with monocular traumatic optic neuropathy who were followed up for over 6 months were retrospectively analyzed. Best-corrected visual acuity was checked and Cirrus high-definition optical coherence tomography (HD-OCT) was used to measure the thicknesses of the peripapillary RNFL, macular GC-IPL, and macula of both eyes at the first visit (within 4 weeks after trauma), at 10 and 24 weeks after trauma, and at the final visits. The differences over time in the parameters of the traumatic and fellow eyes were analyzed. RESULTS: The final best-corrected visual acuities of the traumatic and fellow eyes differed significantly from those at the first visit (p = 0.007). The average thicknesses of the peripapillary RNFL, the macular GC-IPL, and the macula differed significantly between the traumatic and fellow eyes commencing 10 weeks after trauma (p < 0.001, p = 0.002, p = 0.003, respectively). CONCLUSIONS: Significant changes in visual acuity preceded structural changes in the retina. Objective assessment of retinal structural changes using OCT yields helpful information on the clinical course of patients with traumatic optic neuropathy.
Ganglion Cysts ; Humans ; Medical Records ; Nerve Fibers ; Optic Nerve Injuries ; Retina ; Retinaldehyde ; Retrospective Studies ; Tomography, Optical Coherence ; Visual Acuity

PURPOSE: To report the clinical manifestations and computed tomography (CT) findings of patients with a trapdoor type medial orbital wall blowout fracture.METHODS: From March 2009 to October 2016, the clinical records and computed tomography findings of patients who underwent surgical treatment for a trapdoor type medial orbital wall blowout fracture were retrospectively analyzed.RESULTS: A total of eight patients (six males and two females) were enrolled with a combined mean age of 14.4 years. Clinical manifestations were eyeball movement limitation (abduction and adduction) and ocular motility pain (eight patients, 100%), diplopia (seven patients, 87.5%), and nausea and vomiting (four patients, 50%). On CT, the distance from the orbital apex to the fracture site was an average of 22.0 mm and occurred in the middle position of the entire wall. Two patients had missed rectus completely dislocated into the ethmoid sinus through the fracture gap and six patients had definite involvement in the fracture gap and edema of the medial rectus muscle. The medial rectus muscle cross-sectional area was 47.7 mm² which was edematous compared to the contralateral eye (40.1 mm²). Orbital wall reconstruction was performed an average of 4.1 days after the injury. In all patients with oculocardiac reflex-like nausea and vomiting immediately improved after surgery. Six out of eight patients who had eyeball movement limitations (abduction and adduction) preoperatively showed adduction limitation after surgery. The eyeball movement limitation and diplopia disappeared 11.7 days and 46.7 days after surgery, respectively.CONCLUSIONS: Patients with trapdoor type medial wall blowout fracture showed characteristic computed tomographic findings and clinical manifestations such as eyeball movement limitation, ocular motility pain, diplopia, and oculocardiac reflex. An understanding of clinical findings and quick surgical treatment are therefore required. The type of eyeball movement limitation was abduction and adduction limitation preoperatively and adduction limitation postoperatively.
Diplopia ; Edema ; Ethmoid Sinus ; Humans ; Male ; Nausea ; Orbit ; Reflex, Oculocardiac ; Retrospective Studies ; Vomiting

PURPOSE: RKIP (Raf kinase inhibitor protein) is a novel candidate tumor suppressor, known to inhibit the MAPK signaling by interfering with the MEK phosphorylation by Raf-1. The aim of this study was to investigate the expression of RKIP and analyze the pattern of inactivation and mutation of the RKIP gene in human gastric cancer. METHODS: To explore if RKIP inactivation is implicated in gastric tumorigenesis, an expression analysis on the transcription and protein expression levels and a mutational analysis of RKIP were performed in 15 human gastric cancer cell lines and 92 primary carcinoma tissues. RESULTS: Abnormal reduction of the level of RKIP expression was frequently detected in the cancer cell lines and primary tumor tissues, at both the transcript and protein levels. Moreover, the expression level of RKIP in the tumor cells was inversely correlated with the level of Erk phosphorylation, indicating that RKIP plays a key role in the regulation of the Raf-MEK-Erk signaling pathway in human gastric cells. While the expression of the RKIP transcript was not re-activated in low expressor cells by treatment with the demethylating agent 5'Aza-dC, the genomic RKIP was detected at low levels in many cancer cell lines, suggesting that an abnormal reduction of level of RKIP expression in tumors might be caused by allelic deletion of the gene rather than transcriptional silencing due to aberrant DNA hypermethylation. A loss of heterozygosity study, using an intragenic polymorphic marker, revealed that approximately 21% of the gastric cancers harbored allelic loss of the RKIP gene. CONCLUSION: Collectively, this study has demonstrated that RKIP is a tumor suppressor, whose expression is frequently downregulated by allelic deletion in human gastric cancers. This study also suggests that an altered expression of RKIP might contribute to the development of gastric cancer via abnormal elevation of the Raf-Erk signaling pathway.
Carcinogenesis ; Cell Line ; DNA ; Humans* ; Loss of Heterozygosity ; Phosphorylation ; Phosphotransferases* ; Stomach Neoplasms*

OBJECTIVE: Acquisition of a proangiogenic environment is essential to the cervical cancer growth, invasion and metastasis, and the angiogenic phenotype in cervical cancer is strongly associated with clinical outcome. However, the regulation of the metastatic process in cervical cancer has not been well defined. Thrombospondin-1 (TSP-1) is a representative angiogenesis suppressor whose loss or reduced expression has been frequently observed in many types of human neoplasms. In this study, we examined whether expression of TSP-1 is associated with clinicopathological features, including microvessel density and evaluated its prognostic significance in patients with cervical cancer. METHODS: The expression and mutation status of TSP-1 was examined by quantitative RT- and genomic PCR and RT-PCR-SSCP analysis and microvessel density was performed using immunohistochemical staining in 7 normal cervix and 37 cervical cancers. RESULTS: All normal cervix tissues express easily detetable levels of TSP-1 transcript in range of 1.41-1.62 (mean 1.51 +/- 0.07). In contrast to normal tissue, mRNA expression of TSP-1 in primary cancer was detected in range of 0.51-1.69 (mean 1.03 +/- 0.36), and 35.1% (13 of 37) of carcinomas expressed abnormally low levels of TSP-1 (p<0.05). Moreover, abnormal reduction of TSP-1 expression was more frequently observed in IIa-IIb cancer (60%, 6 of 10) compared to Ib cancer (25.9%, 7 of 27) (p<0.05). None of carcinoma tissues we tested showed abnormal reduction of TSP-1 gene level and no evidences for sequence alterations leading to amino acid substitution were identified, indicating that allelic deletion or mutational alteration of TSP-1 might be a rare event in cervical carcinogenesis. Microvessel density was significantly higher in tumors showing decreased expression of TSP-1 (abnormal low group: 11.3 +/- 5.06, others: 6.64 +/- 7.15) (p<0.05). To detect the possible deletion of the gene and the presence of sequence alteration in TSP-1 transcripts, we performed quantitative genomic PCR and RT-PCR-SSCP analysis. However, none of carcinoma tissues we tested showed abnormal reduction of TSP-1 gene level and no evidence for sequence alterations leading to amino acid substitution were identified. CONCLUSION: Our study demonstrates that abnormal reduction of TSP-1 mRNA expression is frequent in cervical cancer and correlates with the malignant progression of cervical cancers. Our data also show that allelic deletion or mutational alteration of TSP-1 is rare in cervical cancers, suggesting that abnormal reduction of TSP-1 mRNA expression in cervical cancers might be caused by altered transcriptional down regulation of the gene, such as epigenetic gene silencing. The inverse correlation between TSP expression and microvessel density also indicates that decreased TSP-1 expression might be associated with an angiogenic phenotype in cervical cancer.
Amino Acid Substitution ; Carcinogenesis ; Cervix Uteri ; Down-Regulation ; Epigenomics ; Female ; Gene Silencing ; Humans ; Microvessels ; Neoplasm Metastasis ; Phenotype ; Polymerase Chain Reaction ; RNA, Messenger* ; Thrombospondin 1* ; Uterine Cervical Neoplasms*

OBJECTIVE: Angiogenesis, the formation of blood vessels by sprouting from pre-existing ones, is essential for the growth of solid tumors beyond 2-3mm in diameter and for tumor metastasis. Vascular endothelial growth factor (VEGF), is known as vascular permeability factor(VPF) and mediates vascularization and tumor-induced angiogenesis. This study examined the potential of growth, invasion, and metastasis of uterine cervical carcinomas associated with neovascularization. METHODS: From January 1996 to December 1999, at the Department of Obstetrics and Gynecology, Kyung-Hee University Hospital, 37 uterine cervical carcinomas and 7 normal cervical tissues were obtained and the samples were immediately frozen and stored at -70 degrees C. Immunohistochemical staining for VEGF was carried out to study VEGF localization, and the levels of VEGF subtype mRNAs were determined by quantitative RT-PCR in specimens. The relation between VEGF subtypes expression of cervical cancers was analysed. RESULTS: The positive staining for VEGF is seen dominantly in the cytoplasm of the cancer cells, and faintly in interstitial cells. The intensity of staining was stronger in squamous carcinomas than in adenocrcinomas, but there was no significant difference (p>0.05). Quantitative RT-PCR analysis demonstrated significantly increased VEGF121/VEGF165 mRNA expression levels (>0.56 / >0.72) in 21 (56.8%) and 15 (40.5%) of 37 cervical carcinomas comparing to control groups (mean: 0.28 / 0.36). There was no obvious relationship between VEGF121/VEGF165 mRNA expression levels and the clinical parameters examined including age, pathology, differentiation, tumor size, lymphovascular space invasion, LN involvement and invasion depth except clinical stage (p<0.05). CONCLUSIONS: The overexpression of VEGF mRNA may be an important contributing factor in cervical carcinomas. There is no significant differenece of VEGF mRNAs levels according to clinical parameters, so it seems that the expression of VEGF is involved in the promotion of angiogenesis on cervical cancer and plays an important role in early invasion.
Blood Vessels ; Capillary Permeability ; Carcinoma, Squamous Cell ; Cytoplasm ; Gynecology ; Neoplasm Metastasis ; Obstetrics ; Pathology ; RNA, Messenger* ; Uterine Cervical Neoplasms ; Vascular Endothelial Growth Factor A*

OBJECTIVE: TGF-beta signaling is dependent on the heterodimerization of the type II TGF-beta receptor (TbetaR-II) with the type I TGF-beta receptor (TbetaR-I). which mediate intracellular signals through Smad proteins. Whereas physiologic concentrations of SnoN and Ski allow a feedback regulation of TGF-beta signaling, deregulation of SnoN or Ski expression leads to total inhibition of TGF-beta signaling and of the tumor suppressors Smad2 and Smad4, which can explain the role of SnoN and Ski as oncogenes. In order to identify possible molecular mechanisms responsible for TGF-beta resistance, the author investigated the mutation and expression of TGF-beta1, its receptors, Ski/SnoN in cervical carcinomas. METHODS: From December 1995 to December 1999, 45 carcinomas and 7 normal cervical tissue specimens were obtained by surgical resection in the Kyung Hee University Medical Center. Tissue specimens were snap-forzen in liquid N2 and stored at -70 degrees C until used. Total RNA was extracted from specimens and evaluated the expression levels using densitometric analysis of quantitative RT-PCR products (TGF-beta1, Tbeta1R-I, Tbeta1R-II, Ski/SnoN), and the mutations were investigated by quantitative genomic-PCR followed by nonisotopic RT-PCR-SSCP analysis (Tbeta1R-II, Tbeta1R-I, Ski/SnoN). The abnorally expressed levels of RT-PCR products (TGF-beta1, Tbeta1R-II) were analysed for the clinicopathologic characteristics. RESULTS: Quantitative RT-PCR analysis demonstrated variable expression of TGF-beta1 mRNA (0.05-0.89) in tumors and significantly increased TGF-beta1 expression level (>0.48) in 15 of 45 samples (33.3%). There is no significant reduction of Tbeta1R-I expression (<0.38) in tumors, but 9 of all tumors (20.0%) show significantly reduced levels of Tbeta1R-II expression (<0.58). Using quantitative DNA-PCR analysis, all of 9 specimens with abnormally low Tbeta1R-II expression show abnormally low levels (<0.47) of the Tbeta1R-II gene at genomic level which suggests allelic deletion of the gene in these specimens. Gene mutations of TGF-beta1 receptors were analysed using specific primers by RT-PCR-SSCP analysis, and the results revealed no mutational alterations of TGF-beta1 receptors and no mutation in poly (A) region of Tbeta1R-II. Quantitative RT-PCR analysis demonstrated variable expression of Ski/SnoN (0.65-1.46/0.75-1.62) in tumors and significantly increased Ski expression level (>1.36) in 2 of 45 samples (4.4%), and there is no amplification of Ski/SnoN gene by quantitative genomic-PCR analysis. CONCLUSIONS: The overexpression of TGF-beta1 mRNA and the reduced or absent expression of Tbeta1R-II may be an important contributing factors, and the abnormally low genomic levels and no mutational alterations of Tbeta1R-II is caused by monoallelic deletion suggesting that Tbeta1R-II might play as a tumor suppressor of haloinsufficiency in cervical carcinomas. We could not show that high levels of Ski/SnoN expression could produce a disruption of TGF-beta signaling in cervical carcinomas.
Academic Medical Centers ; Oncogenes ; Receptors, Transforming Growth Factor beta ; RNA ; RNA, Messenger* ; Smad Proteins ; Transforming Growth Factor beta* ; Transforming Growth Factor beta1

OBJECTIVE: X-linked inhibitor of apoptosis (XIAP) is the most potent member of IAP family that exerts antiapoptotic effects by interfering with activities of caspases. Recently, XIAP-associated factor 1 (XAF1) and two mitochondrial proteins, Smac/DIABLO and HtrA2, have been identified to negatively regulate the caspase-inhibiting activity of XIAP. We explore the candidacy of XAF1, Smac/DIABLO and HtrA2 as a tumor suppressor in cervical carcinogenesis and determine the mechanisms of altered XAF1 expression. METHODS: We investigated the expression and mutation status of the genes in 64 cervical cancer tissues, 5 cervical cancer cell lines and 10 normal cervical tissues. RESULTS: XAF1 transcript was not expressed or extremely low levels in 40% (2/5) of cancer cell line and in 31% (20/64) of primary carcinomas whereas Smac/DIABLO and HtrA2 are normally expressed in all cells. As somatic mutations of the gene was not detected, expression of XAF1 transcript was reactivated in all nonexpressor cell lines after 5-aza-2-deoxycytidine treatment. Bisulfite DNA analysis for CpG sites in the promoter region revealed a strong association between CpG sites hypermethylation and gene silencing. CONCLUSION: XAF1 undergoes epigenetic silencing in a considerable proportion of cervical carcinomas by aberrant promoter hypermethylation rather than genetic alterations, and closely associated with reduced gene expression. Although additional studies are required to determine the biological significance of XAF1 inactivation, it will be valuable to examine the expression status of XAF1 could be a clinically useful marker for cancer treatment.
Apoptosis ; Carcinogenesis ; Caspases ; Cell Line ; DNA ; Epigenomics* ; Gene Expression ; Gene Silencing ; Humans* ; Mitochondrial Proteins ; Promoter Regions, Genetic ; Uterine Cervical Neoplasms

OBJECTIVE: Measure the over-expression of p73 and analyze as the prognostic as well as angiogenic factor of cervical cancer by comparing the degree of expression of VEGF and TSP-1 by RT-PCR. METHODS: 7 normal and 37 cervical cancer specimens were put through RT-PCR and the expression of p73, VEGF and TSP-1 were measured. After immunohistochemical staining, the number of microvessels was counted. With the level of expression, investigated the relationship with the clinicopathological characteristics and the number of microvessels. RESULTS: 57% of cancer tissues showed abnormally high levels of p73 mRNA. In quantitative genomic DNA PCR, the p73 was over-expressed in the transcription level. Through allotyping with Sty I polymorphism, the over-expression of p73 was due to the transcription activity of the silent allele. In RT-PCR-SSCP analysis of over-expressed specimens, sequence alterations was not seen. In 73%, VEGF was over-expressed while TSP-1 was under-expressed in 35%. There was no association between the number of microvessels with the over-expression of p73 and VEGF, but inversely associated with the under-expression of TSP-1. There was no correlation between the over-expression of p73 and the clinicopathological characteristics. The over-expression of p73 coincided 80% with the over-expression of VEGF, and 40% with the under-expression of TSP-1. CONCLUSION: These data support the expression of p73 was increased in cervical cancer tissues and was associated with the over-expression of the VEGF but not associated with the under-expression of TSP-1. The biological and clinical significance of the over-expression of p73 should be studied further in the future.
Alleles ; Angiogenesis Inducing Agents ; DNA ; Microvessels ; Polymerase Chain Reaction ; RNA, Messenger ; Thrombospondin 1* ; Uterine Cervical Neoplasms ; Vascular Endothelial Growth Factor A*