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Low-grade Tumors (low-grade + tumor)
Selected AbstractsMucosa-associated lymphoid tissue lymphoma: Molecular pathogenesis and clinicopathological significancePATHOLOGY INTERNATIONAL, Issue 8 2007Hiroshi Inagaki Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade tumor closely associated with chronic inflammation such as that of Helicobacter pylori gastritis, Sjogren's syndrome, and Hashimoto's thyroiditis. Tumor regression by H. pylori eradication alone is well known in gastric MALT lymphoma, but some tumors occur in the absence of pre-existing chronic inflammation. The understanding of MALT lymphoma biology has significantly improved, and recurrent cytogenetic alterations have been detected. These include the trisomies 3 and 18, and the translocations t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). At least some of these alterations result in the constitutive activation of the nuclear factor (NF)-,B pathway, and may exert anti-apoptotic action. Apoptosis inhibitor 2,MALT lymphoma-associated translocation 1 (API12 - MALT1) fusion, resulting from t(11;18)(q21;q21), is specific to, and is the most common in, MALT lymphomas, and its clinicopathological significance has been studied extensively. The focus of the present review is on the recent progress made in elucidating MALT lymphomagenesis and its clinicopathological impact, especially in terms of the effect of API2-MALT1 fusion on this unique tumor. [source] Ceramide levels are inversely associated with malignant progression of human glial tumorsGLIA, Issue 2 2002Laura Riboni Abstract Ceramide represents an important sphingoid mediator involved in the signaling pathways that control cell proliferation, differentiation, and death. To determine whether ceramide levels correlate with the malignant progression of human astrocytomas, we investigated these levels in surgical specimens of glial tumors of low-grade and high-grade malignancy. Tumor samples obtained from 52 patients who underwent therapeutic removal of primary brain tumors were used. The tumors were classified according to standard morphologic criteria and were grouped into tumors of low-grade and high-grade malignancy. Sections of normal brain tissue adjacent to the tumor were also analyzed in 11 of the 52 patients. After extraction and partial purification, ceramide was measured by quantitative derivatization to ceramide-1-phosphate using diacylglycerol kinase and [,- 32P]ATP. Ceramide levels were significantly lower in the combined high-grade tumors compared with low-grade tumors and in both tumor groups compared with peritumoral tissue. The results indicate an inverse correlation between the amount of ceramide and tumor malignancy as assessed by both the histological grading and ganglioside pattern. Moreover, overall survival analysis of 38 patients indicates that ceramide levels are significantly associated with patient survival. The present findings indicate that ceramide is inversely associated with malignant progression of human astrocytomas and poor prognosis. The downregulation of ceramide levels in human astrocytomas emerges as a novel alteration that may contribute to glial neoplastic transformation. The low ceramide levels in high-grade tumors may provide an advantage for their rapid growth and apoptotic resistant features. This study appears to support the rationale for the potential benefits of a ceramide-based chemotherapy. GLIA 39:105,113, 2002. © 2002 Wiley-Liss, Inc. [source] Significance of Fas expression alteration during tumor progression of renal cell carcinomaINTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2006TAKEHIRO SEJIMA Background:, In order to characterize the alteration of apoptotic regulatory molecule expression during tumor progression of renal cell carcinoma (RCC), we compared the expression between tumor and normal tissues, and evaluated the relationship of the expression in tumors with pathological and clinical characteristics. Methods:, Competitive reverse transcription,polymerase chain reaction (RT,PCR) and immunohistochemistry (IHC) allowed the determination of Fas and bcl-2 mRNA and protein expression in surgically resected tumor and normal tissue of 50 RCC. Results:, The mRNA expression of Fas and bcl-2 in RCC was significantly reduced compared to that in normal tissues. An IHC analysis was supportive of the RT,PCR results. In terms of relationships with pathological and clinical characteristics, the mRNA and protein expression of Fas in high-stage or high-grade tumors was significantly higher than that in low-stage or low-grade tumors. Moreover, a statistically poor prognosis was observed in tumor cases expressing a high amount of mRNA. In bcl-2 analysis, the mRNA and protein expression was significantly reduced in clear cell tumors compared to chromophobe cell tumors. Conclusion:, It is suggested that the reduced expression of Fas and bcl-2 in RCC compared with the expression in normal kidney is a prominent alteration of apoptotic regulatory molecules. The alteration of the up-regulated Fas expression might be characterized during the tumor progression stage. It is also suggested that the effect of alteration of bcl-2 expression might be minimal during the tumor progression stage because of the reduced expression in tumors of the clear cell type, which is the most dominant cell type in RCC. [source] Proton magnetic resonance spectroscopic imaging to differentiate between nonneoplastic lesions and brain tumors in children,JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 2 2006Roula Hourani MD Abstract Purpose To investigate whether in vivo proton magnetic resonance spectroscopic imaging (MRSI) can differentiate between 1) tumors and nonneoplastic brain lesions, and 2) high- and low-grade tumors in children. Materials and Methods Thirty-two children (20 males and 12 females, mean age = 10 ± 5 years) with primary brain lesions were evaluated retrospectively. Nineteen patients had a neuropathologically confirmed brain tumor, and 13 patients had a benign lesion. Multislice proton MRSI was performed at TE = 280 msec. Ratios of N-acetyl aspartate/choline (NAA/Cho), NAA/creatine (Cr), and Cho/Cr were evaluated in the lesion and the contralateral hemisphere. Normalized lesion peak areas (Chonorm, Crnorm, and NAAnorm) expressed relative to the contralateral hemisphere were also calculated. Discriminant function analysis was used for statistical evaluation. Results Considering all possible combinations of metabolite ratios, the best discriminant function to differentiate between nonneoplastic lesions and brain tumors was found to include only the ratio of Cho/Cr (Wilks' lambda, P = 0.012; 78.1% of original grouped cases correctly classified). The best discriminant function to differentiate between high- and low-grade tumors included the ratios of NAA/Cr and Chonorm (Wilks' lambda, P = 0.001; 89.5% of original grouped cases correctly classified). Cr levels in low-grade tumors were slightly lower than or comparable to control regions and ranged from 53% to 165% of the control values in high-grade tumors. Conclusion Proton MRSI may have a promising role in differentiating pediatric brain lesions, and an important diagnostic value, particularly for inoperable or inaccessible lesions. J. Magn. Reson. Imaging 2006. Published 2005 Wiley-Liss, Inc. [source] Liver grafts from donors with central nervous system tumors: A single-center perspectiveLIVER TRANSPLANTATION, Issue 10 2009Randeep Kashyap Traditionally, patients who die with a malignancy have been excluded from donation. However, it has become a common practice to accept organs from donors that have low-grade tumors or tumors with low metastatic potential. The aim of this study was to analyze our experience with the use of liver grafts from donors with central nervous system (CNS) tumors. A retrospective review of 1173 liver transplants performed between 1992 and 2006 identified 42 donors diagnosed with a CNS tumor. Thirty-two tumors were malignant, and 10 tumors were benign. Forty-two liver transplant recipients received livers from these donors. All patients were followed until May 2007 with a mean follow-up of 29 ± 17 months. Among 42 donors, there were 28 males and 14 females. The mean donor risk index was 1.78 ± 0.39. Twenty (47.6%) of the CNS tumors were glioblastoma multiforme (astrocytoma grade IV), 11 (26.2%) were other astrocytomas, and 1 (2.4%) was an anaplastic ependymoma. Twenty (62.5%) neoplasms were grade IV tumors, 8 (25%) were grade II tumors, and 4 (12.5%) were grade III tumors. Over 80% of the patients had at least 1 kind of invasive procedure violating the blood-brain barrier. The rate of recurrence for the entire group was 2.4% (all CNS tumors). There were 7 (7.2%) deaths in all. The most common cause of death was sepsis (n = 3, 7.2%). There was no difference in survival between recipients of grafts from donors with CNS tumors and recipients of grafts from donors without CNS tumors (1 year: 82% versus 83.3%, P = not significant; 3 years: 77.4% versus 72%, P = not significant). In conclusion, in our experience, despite violation of the blood-brain barrier and high-grade CNS tumors, recurrence was uncommon. Grafts from these donors are often an overlooked source of high-quality organs from younger donors and can be appropriately used, particularly in patients who, despite low Model for End-Stage Liver Disease scores, carry a high risk of mortality. Liver Transpl 15:1204,1208, 2009. © 2009 AASLD. [source] Characterization of oligodendrogliomas using short echo time 1H MR spectroscopic imagingNMR IN BIOMEDICINE, Issue 1 2003M. Rijpkema Abstract Oligodendroglial tumors may not be distinguished easily from other brain tumors based on clinical presentation and magnetic resonance imaging (MRI) alone. Identification of these tumors however may have therapeutic consequences. The purpose of this study was to characterize and identify oligodendrogliomas by their metabolic profile as measured by 1H MR spectroscopic imaging (MRSI). Fifteen patients with oligodendroglial tumors (eight high-grade oligodendrogliomas, seven low-grade oligodendrogliomas) underwent MRI and short echo time 1H MRSI examinations. Five main metabolites found in brain MR spectra were quantified and expressed as ratios of tumor to contralateral white matter tissue. The level of lipids plus lactate was also assessed in the tumor. For comparison six patients with a low grade astrocytoma were also included in the study. The metabolic profile of oligodendrogliomas showed a decreased level of N -acetylaspartate and increased levels of choline-containing compounds and glutamine plus glutamate compared with white matter. The level of glutamine plus glutamate was significantly higher in low-grade oligodendrogliomas than in low-grade astrocytomas and may serve as a metabolic marker in diagnosis and treatment planning. In high-grade oligodendrogliomas large resonances of lipids plus lactate were observed in contrast to low-grade tumors. Copyright © 2003 John Wiley & Sons, Ltd. [source] Aberrant Hypermethylation of p14ARF and O6 -methylguanine-DNA Methyltransferase Genes in Astrocytoma ProgressionBRAIN PATHOLOGY, Issue 1 2007Takao Watanabe MD The aim of the present study was to elucidate genetic alterations that are critically involved in astrocytoma progression. We characterized 27 World Health Organization grade II fibrillary astrocytomas which later underwent recurrence or progression, paying specific attention to the CpG island methylation status of critical growth regulatory genes. p14ARF and O6 -methylguanine-DNA methyltransferase (MGMT) hypermethylation represented frequent events (26% and 63%, respectively), which were mutually exclusive except in one case, with alternate or simultaneous methylation of these two genes occurring in 85% of our tumor series. Seventeen tumors (63%) contained TP53 mutations, which were closely related to the presence of MGMT methylation. Methylation of the p21Waf1/Cip1, p27Kip1 and p73 genes and homozygous deletion of the p16INK4a, p15INK4b and p14ARF genes were not detected in any of the primary low-grade tumors. The presence of p14ARF methylation at first biopsy was associated with shorter patient survival, whereas the presence of MGMT methylation carried a better clinical outcome after salvage therapy. Examination of 20 cases whose histological data for recurrent tumors were available revealed that malignant progression occurred in all of the tumors with p14ARF methylation but less frequently (50%) in the lesions with MGMT methylation. On analysis of their respective recurrent tumors, five of six patients whose primary low-grade tumors carried p14ARF methylation exhibited homozygous co-deletions of the p14ARF, p15INK4b and p16INK4a genes, which were restricted to glioblastoma as the most malignant end point. Our findings suggest that p14ARF hypermethylation and MGMT hypermethylation constitute distinct molecular pathways of astrocytoma progression, which could differ in biological behavior and clinical outcome. [source] Germ cell-specific heat shock protein 70-2 is expressed in cervical carcinoma and is involved in the growth, migration, and invasion of cervical cellsCANCER, Issue 16 2010Manoj Garg PhD Abstract BACKGROUND: Cervical cancer is a major cause of death among women worldwide, and the most cases are reported in the least developed countries. Recently, a study on DNA microarray gene expression analysis demonstrated the overexpression of heat shock protein 70-2 (HSP70-2) in cervical carcinoma cells (HeLa). The objective of the current study was to evaluate the association between HSP70-2 expression in cervical carcinogenesis and its potential role in various malignant properties that result in disease progression. METHODS: HSP70-2 expression was examined in various cervical cancer cell lines with different origins and in clinical cervical cancer specimens by reverse transcriptase-polymerase chain reaction (RT-PCR), flow cytometry, and immunohistochemistry (IHC) analyses. A plasmid-based, short-hairpin RNA approach was used specifically to knock down the expression of HSP70-2 in cervical tumor cells in vitro and in vivo to examine the role of HSP70-2 on various malignant properties. RESULTS: RT-PCR and IHC analyses revealed HSP70-2 expression in 86% of cervical cancer specimens. Furthermore, knockdown of HSP70-2 expression significantly reduced cellular growth, colony formation, migration, and invasion in vitro and reduced tumor growth in vivo. A significant association of HSP70-2 gene and protein expression was observed among the various tumor stages (P = .046) and different grades (P = .006), suggesting that HSP70-2 expression may be an indicator of disease progression. CONCLUSIONS: The current findings suggested that HSP70-2 may play an important role in disease progression in cervical carcinogenesis. Patients who had early stage disease and low-grade tumors had HSP70-2 expression, supporting its potential role in early detection and aggressive treatment modalities for cervical cancer management. Cancer 2010. © 2010 American Cancer Society. [source] The role of postoperative radiotherapy for the treatment of gangliogliomasCANCER, Issue 2 2010Dirk Rades MD Abstract BACKGROUND: Because of their rarity, no prospective studies have been performed regarding gangliogliomas. The optimal treatment regimen is unclear. In this study, the authors compared 4 therapies for local control (LC) and overall survival (OS) in patients with ganglioglioma. METHODS: In 402 patients with ganglioglioma, outcomes were compared for patients who underwent gross total resection alone (GTR) (n = 188), GTR plus radiotherapy (GTR + RT) (n = 21), subtotal resection alone (STR) (n = 113), and STR plus RT (STR + RT (n = 80). Age, sex, tumor site, and histologic grade also were investigated. Subgroup analyses were performed for both low-grade and high-grade tumors. RESULTS: The 10-year LC rates were 89% after GTR, 90% after GTR + RT, 52% after STR, and 65% after STR + RT (P < .001); and the 10-year OS rates were 95%, 95%, 62%, and 74%, respectively (P < .001). After STR, irradiation significantly improved LC (P = .004) but not OS (P = .22). After GTR, irradiation did not significantly improve LC (P = .23) or OS (P = .29). On multivariate analyses, LC and OS were associated with therapy and pathologic grade, and OS also was associated with tumor site. In low-grade tumors, STR + RT resulted in better LC (P = .016) but not better OS (P = .18); and, after GTR, LC (P = .28) and OS (P = 1.0) were not improved with postoperative radiotherapy. In high-grade tumors, STR + RT resulted in better LC (P = .016) but not better OS (P = .41); after GTR, LC (P = .56) and OS (P = .61) were not improved with irradiation. CONCLUSIONS: According to this review, GTR should be performed whenever safely possible and does not require postoperative irradiation. If only STR is achieved, then RT improves LC of both low-grade and high-grade tumors and, thus, should be considered seriously. Cancer 2010. © 2010 American Cancer Society. [source] Chromophobe renal cell carcinomaCANCER, Issue 7 2004Analysis of 61 cases Abstract BACKGROUND Chromophobe renal cell carcinoma (CRCC) is often associated with a favorable prognosis. However, to the authors' knowledge, only few clinical data are available regarding this variant of tumor. In the current study, the authors report their experience with CRCC over the last 14 years. METHODS Since 1989, 61 patients have been treated at the study institution for CRCC. Tumor characteristics and patient outcome were analyzed retrospectively. Data were obtained from the patients' medical records. RESULTS The mean age of the patients was 58 years. Of the 61 tumors, 68.8% were discovered incidentally. The mean tumor size was 6.9 cm. Fifty-seven patients (93.4%) were treated with radical nephrectomy and 4 patients (6.6%) underwent partial nephrectomy. According to the 1997 TNM classification, the pathologic tumor stage was T1 in 65.6% of cases, T2 in 31.1% of cases, and T3a in 3.3% of cases. All tumors were staged as N0M0. Nuclear grade was low (1 or 2) in 88.5% of cases. In no case of CRCC was a sarcomatoid component observed. At a mean follow-up of 49.5 months (range, 5,135 months), no patient had experienced tumor recurrence or disease progression, and none had died of renal carcinoma. CONCLUSIONS In the authors' experience, CRCC carries an excellent prognosis, possibly due to the high rate of low-stage and low-grade tumors. Cancer 2004;100:1406,10. © 2004 American Cancer Society. [source] Expression of c-ABL, c-KIT, and platelet-derived growth factor receptor-, in ovarian serous carcinoma and normal ovarian surface epitheliumCANCER, Issue 4 2003Rosemarie E. Schmandt Ph.D. Abstract BACKGROUND Tyrosine kinases, such as c-KIT, c-ABL, and platelet-derived growth factor-beta (PDGFR-,), are important regulators of cell growth. Highly potent and selective inhibitors of tyrosine kinases are being investigated as alternatives to standard chemotherapy. One such inhibitor, imatinib mesylate, is being used to treat gastrointestinal stromal tumors and chronic myelogenous leukemia. Ovarian carcinomas frequently develop resistance to conventional chemotherapeutic agents. Immunohistochemical expression of c-ABL, PDGFR-,, and c-KIT was evaluated in ovarian carcinomas to determine whether treatment with imatinib mesylate might be feasible. METHODS The expression of c-ABL, c-KIT, and PDGFR-, in tumors was evaluated by immunohistochemical analysis of 52 ovarian serous carcinomas, including 21 low-grade (well differentiated) and 31 high-grade (poorly differentiated) tumors. Fourteen normal ovaries were also evaluated. RESULTS In normal ovarian surface epithelium, c-ABL was expressed universally. PDGFR-, was expressed in the majority (93%) of samples of normal ovarian epithelium, whereas the c-KIT protein was undetectable in normal ovarian surface epithelium. Overall, c-ABL was expressed in 71% of serous carcinomas. c-ABL was expressed more frequently in the low-grade serous carcinomas (81%) compared with the high-grade serous carcinomas (65%). PDGFR-, expression was observed in 81% of serous carcinomas overall and was observed more frequently in higher-grade tumors. c-KIT immunohistochemical staining was absent in low-grade tumors but was present in 26% of high-grade serous carcinomas. CONCLUSIONS The majority of ovarian serous carcinomas express one or more of the kinases targeted by the tyrosine kinase inhibitor, imatinib mesylate, suggesting the potential usefulness of this drug in the treatment of ovarian carcinoma. Cancer 2003;98:758,64. © 2003 American Cancer Society. DOI 10.1002/cncr.11561 [source] Chromosomal anomalies in oligodendroglial tumors are correlated with clinical featuresCANCER, Issue 5 2003M.D., Martin J. van den Bent Ph.D. Abstract BACKGROUND Patients who have oligodendrogliomas (OD) that demonstrate loss of both 1p and 19q appear to have a better prognosis after they receive chemotherapy and radiotherapy compared with patients who have OD without these characteristics. It is unclear whether this improvement in outcome is due only to a better response to treatment. The authors investigated the correlation between genetic and clinical characteristics of OD in 33 patients who received chemotherapy with procarbazine, lomustine, and vincristine for recurrent disease after receiving radiotherapy. METHODS The initial presentation, prior treatments, overall survival, and response to chemotherapy were assessed. The 1p and 19q status in OD lesions was determined with fluorescence in situ hybridization on paraffin embedded, archival material using locus specific probes. P53 mutations were assessed by polymerase chain reaction,single-strand conformation polymorphism analysis and immunohistochemistry for P53; the proliferation index was assessed with the MIB-1 antibody. RESULTS Patients who had OD lesions with a combined loss of 1p and 19q typically presented with low-grade tumors that manifested with seizures of long-standing duration. In contrast, patients who had OD lesions without a combined loss of 1p and 19q usually presented with focal deficits that required immediate treatment. Both the response rate to chemotherapy and the time to disease progression after chemotherapy were significantly better in patients who had a combined loss of 1p and 19. Tumors with classic OD morphology more often had a combined loss of 1p and 19q, although the genotype was better at identifying patients with chemoresponsive tumors. P53 mutations were observed in three tumors, none of which had a combined loss of 1p and 19q. CONCLUSIONS OD lesions with combined a loss of 1p and 19q have a more indolent nature compared with OD lesions that do not have these losses. Virtually all patients with these tumors present with low-grade tumors accompanied by seizures and remain stable for prolonged periods. Future trials must keep these tumor types apart. Cancer 2003;97:1276,84. © 2003 American Cancer Society. DOI 10.1002/cncr.11187 [source] Dynamic alterations of the extracellular environment of ovarian surface epithelial cells in premalignant transformation, tumorigenicity, and metastasisCANCER, Issue 8 2002Callinice D. Capo-Chichi Ph.D. Abstract BACKGROUND Ovarian surface epithelial cells are positionally organized as a single cell layer by a sheet of basement membrane. It is believed that the contact of the ovarian surface epithelial cells with the basement membrane regulates cell growth and ensures the organization of the epithelium. Disabled-2 (Dab2), a signal transduction protein and a candidate tumor suppressor of ovarian carcinoma, functions in positional organization of ovarian surface epithelial cells. In ovarian carcinomas, genetic and epigenetic changes enable the tumor cells to escape positional control and proliferate in a disorganized fashion. Alterations in the extracellular environment may also be critical for tumor initiation and progression. METHODS We analyzed and compared the presence of collagen IV and laminin, the scaffold proteins of the basement membrane, and Dab2 in 50 ovarian tumors that are restricted to the ovaries and in 50 metastases of ovarian tumors by immunohistochemistry. Expression of collagen IV, laminin, and Dab2 was also analyzed by Northern blotting in a panel of human ovarian surface epithelial and cancer cell lines. RESULTS The basement membrane is often absent in morphologically benign ovarian surface and cyst epithelium and low-grade tumors and collagen IV and laminin are absent in the extracellular matrix of most of the primary tumors tested. Of the 50 ovarian tumors confined to the ovaries, 6% (3 of 50) were collagen IV positive and 24% (12 of 50) were laminin positive tumors. Of the 50 metastatic tumors, 16% (8 of 50) are collagen IV positive and 86% (43 of 50) are laminin positive. In addition, even in the metastatic ovarian tumors that are largely collagen IV negative, there are pockets of local areas in which the tumor cells are surrounded by collagen IV-positive staining. Dab2 is absent in the majority of ovarian tumors found in both ovaries and metastatic sites. In both nontumorigenic human ovarian surface epithelial and cancer cell lines, collagen IV, laminin, and Dab2 are expressed aberrantly. CONCLUSIONS Loss of the basement membrane may be an early event in the preneoplastic transformation of ovarian surface epithelium and in the early stages of tumorigenesis before tumor invasion and metastasis. The majority of primary ovarian tumors examined lack collagen IV and laminin in their extracellular matrix. However, expression of laminin is restored in the majority of metastatic tumors. Reexpression of collagen IV may also contribute to tumor metastasis. The ability of tumor cells to dynamically alter the expression of collagen IV and laminin may facilitate the shedding of cancer cells into the peritoneal spaces and subsequent attachment to the metastatic sites. We propose that loss of collagen IV and laminin may be an initial event in ovarian tumorigenicity and that restoration of collagen IV and laminin expression in the later stages of tumor development may promote metastasis of ovarian tumors. Cancer 2002;95:1802,15. © 2002 American Cancer Society. DOI 10.1002/cncr.10870 [source] | ||||||||||