National Cancer Institute®
Last Modified: November 21, 2001
UI - 21256548
AU - Cappello F; Barnes L
TI - Synovial sarcoma and malignant mesothelioma of the pleura: review, differential diagnosis and possible role of apoptosis.
SO - Pathology 2001 May;33(2):142-8
AD - Institute of Pathological Anatomy, University of Palermo, Italy. email@example.com
Synovial sarcoma of the pleural cavity is exceptionally rare and may be confused, both clinically and histologically, with malignant mesothelioma, with subsequent inappropriate therapy. To address this dilemma, four biphasic synovial sarcomas (BSSs) and four biphasic malignant mesotheliomas (BMMs) were studied with a panel of mucin and immunohistochemical stains to determine if they would allow one to distinguish between the two. The BMMs were all pleural-based. The BSSs were extrapleural. The mucin and immunohistochemical stains were all performed on formalin-fixed, paraffin-embedded tissue using standard techniques, with appropriate positive and negative controls. Mucin present in BSS is, in general, mucicarmine-positive and resistant to both hyaluronidase and diastase. Of the immune markers evaluated, only calretinin, Ber-Ep4 and bcl-2 were of limited discriminatory value. Subsets of cytokeratins, CEA and CD 34 were not helpful. With the exception of bcl-2, the apoptotic markers p53, bax and cpp32 (caspase) also were not useful. However, when the apoptotic stains were viewed collectively, variations in expression between the two tumours raised the possibility that alterations in apoptotic activity might be responsible for their pathogenesis and behavior. The diagnosis of BSS or BMM of the pleural should be made only after total consideration of clinical, radiological, histochemical and immunohistochemical findings. Although mucin stains are useful in differential diagnosis, reliance solely on immunohistochemical markers, with the possible exception of calretinin, Ber-Ep4 and bcl-2, is not dependable. The role of apoptosis in the pathogenesis of these tumours needs to be explored with a much larger series.
UI - 21256550
AU - Tse GM; Law BK; Chan KF; Mas TK
TI - Multinucleated stromal giant cells in mammary phyllodes tumours.
SO - Pathology 2001 May;33(2):153-6
AD - Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Hong Kong SAR, China. firstname.lastname@example.org
Mammary phyllodes tumour (PT) is an uncommon fibroepithelial neoplasm with a prominent stromal component. We report five cases of PT (one benign, three borderline, one malignant) with giant cells in the stroma. All occurred in adults and ranged from 1.8 to 4.0 cm in size. The overall cellularity, stromal cell pleomorphism and mitotic count was higher for the malignant and borderline than the benign PT. The giant cell number ranged from 18 to 35 cells per 10 high power fields, but there was no relationship between this number and the grade of the PT. Most giant cells were subepithelial, with multiple nuclei arranged in a linear or irregular pattern, and moderate amount of cytoplasm. The immunohistochemical profile of the giant cells was similar to the stromal cells. In all cases, both giant cells and stromal cells expressed vimentin strongly but not desmin; in two cases, both cell populations expressed actin weakly. The respective percentage of giant cells and stromal cells expressing MIB1 was also similar. This suggests that these giant cells do not represent a different, more active stromal population, despite the more bizarre appearance. In view of the small number of cases, the significance of such giant cells on the prognosis of PT remains uncertain.
UI - 21267675
AU - Calle Y; Palomares T; Castro B; del Olmo M; Alonso-Varona A
TI - Removal of N-glycans from cell surface proteins induces apoptosis by reducing intracellular glutathione levels in the rhabdomyosarcoma cell line S4MH.
SO - Biol Cell 2000;92(8-9):639-46
AD - Department of Cell Biology and Morphological Sciences, School of Medicine and Odontology, University of the Basque Country, Leioa, Vizcaya, Spain.
Expression of determined Asn-bound glycans (N-glycans) in cell surface glycoproteins regulates different processes in tumour cell biology. Specific patterns of N-glycosylation are displayed by highly metastatic cells and it has been shown that inhibition of N-glycan processing restrains cell proliferation and induces cell death via apoptosis. However, the mechanisms by which different N-glycosylation states may regulate cell viability and growth are not understood. Since malignant cells express high levels of intracellular glutathione (GSH) and a reduction of intracellular GSH induces cell death via apoptosis, we investigated whether GSH was involved in the induction of apoptosis by removal of cell surface N-glycans. We found that removal of N-glycans from cell surface proteins by treating the rhabdomyosarcoma cell line S4MH with tunicamycin or N-glycosidase resulted in a reduction in intracellular GSH content and cell death via apoptosis. Moreover, GSH depletion caused by the specific inhibitor of GSH synthesis BSO induced apoptosis in S4MH cells. This data indicates that adequate N-glycosylation of cell surface glycoproteins is required for maintenance of intracellular GSH levels that are necessary for cell survival and proliferation.
UI - 21338546
AU - Park YK; Park HR; Chi SG; Ushigome S; Unni KK
TI - Overexpression of p53 and absent genetic mutation in clear cell chondrosarcoma.
SO - Int J Oncol 2001 Aug;19(2):353-7
AD - Department of Pathology, Kyung Hee University Hospital, #1 Hoeki-dong, Dongdaemoon-ku, Seoul 130-702, Korea. email@example.com
Clear cell chondrosarcoma is one of the extremely rare chondrosarcomas. The pathogenesis and the molecular genetic events, which contribute to the development of clear cell chondrosarcoma, are not well elucidated, due in part to the lack of sufficient tumor tissue available. To characterize the involvement of the p53 gene abnormality in this disease, we analyzed expression and sequence alteration of p53 by immunohistochemical analysis of the protein expression and quantitative DNA/PCR and PCR-SSCP assays of the gene in 28 paraffin-embedded tissue specimens. Immunohistochemical analysis demonstrated that 7 (25%) showed patchy positive nuclear staining for p53 and 5 (18%) showed diffuse positive nuclear staining patterns. Sixteen (57%) were negative for p53 immunostaining. Quantitative DNA/PCR analysis revealed that none of the cases we studied showed significantly reduced levels of p53 amplification (<0.50), strongly suggesting an allelic deletion of the p53 gene. In contrast, however, DNA/PCR-SSCP analysis failed to detect any types of mutations resulting in amino acid substitution within exons 5-9 regions of the gene. Taken together, our data suggest that genetic alteration of p53 is a relatively rare event in clear cell chondrosarcomas but a substantial fraction of this type of tumors carries abnormal overexpression of p53, which might result from an as yet unidentified mechanism(s).
UI - 21372582
AU - Barile A; Caulo M; Zugaro L; Di Cesare E; Gallucci M; Masciocchi C
TI - [Staging and re-staging of soft tissue sarcoma using MRI. Usefulness of contrast media]
SO - Radiol Med (Torino) 2001 Jun;101(6):444-55
AD - Cattedra di Radiologia, Universita degli Studi, L'Aquila, Italy. antonio firstname.lastname@example.org
PURPOSE: This study aims to evaluate the usefulness of paramagnetic contrast medium (Gadolinium) in the staging and re-staging of soft tissue tumors using Magnetic Resonance Imaging (MRI). MATERIAL AND METHODS: Sixty patients affected by soft tissue sarcoma of different histotype were retrospectively evaluated. Age ranged from 23 to 78 years. Data were obtained from the musculoskeletal tumor database of our Department of Radiology and cases from the last 7 years (1993-1999) entered this study. All the patients were submitted to ultrasound (US) and to routine and enhanced MR examinations (SE T1-weighted and Fast-SE T1 and T2-weighted before and after fat saturation pulse; GE T2-weighted sequences). At least two different scan planes were obtained depending on the major axis of the lesion. Once imaging information had been obtained all the patients underwent surgery and histology. After surgery, the mean follow-up period was 18 months. Paramagnetic contrast medium (0,2mmol/Kg) was administered in all the MR follow-up examinations. RESULTS: Lesions included adipose histology in 15 cases; muscular histology in 12 cases; fibro-hystiocitic histology in 20 cases; synovial histology in 8 cases; mixed histology in 5 cases. Excluding lesions with mainly adipose content showing obvious high signal intensity on T1-weighted sequences, the other lesions rarely presented MR features specific to histological category also after contrast medium administration. In all the cases MRI allowed an accurate definition of the lesion boundaries to exclude or demonstrate neighbor region invasion. In 11 cases, MRI was able to demonstrate the presence of a recurrent tumor. In 2 out of 11 cases, recurrences were detected out only after intravenous administration of Gadolinium, plain MRI having failed to recognize them. DISCUSSION AND CONCLUSIONS: Despite the absence of specific MRI signs of the different soft tissue tumor histotypes also after Gadolinium administration, MRI remains the best imaging technique to establish the exact morphology of the lesions and to establish the invasion of the neighbor regions by the tumors. The presence of regional spreading of the tumor has to be considered a sign of malignancy. During the follow-up, the use of Gadolinium allows the MR examinations to reach high sensitivity levels and makes it also possible to recognize local recurrences of a very small size. Considering our experience we recommend, whenever a follow-up of resected soft tissue tumors is requested, to perform MRI examination before and after intravenous Gadolinium administration.
UI - 21385121
AU - Koizumi K; Shimamoto Y; Azuma A; Wataya Y; Matsuda A; Sasaki T;
TI - Fukushima M Cloning and expression of uridine/cytidine kinase cDNA from human fibrosarcoma cells.
SO - Int J Mol Med 2001 Sep;8(3):273-8
AD - The Second Cancer Laboratory, Taiho Pharmaceutical Co., Ltd., 1-27 Misugidai, Hanno-city, Saitama 357-8527, Japan.
Uridine/cytidine kinase which converts uridine and cytidine to their corresponding monophosphates is a rate-limiting enzyme involved in the salvage pathway of pyrimidine synthesis. We isolated cDNA encoding the enzyme from human fibrosarcoma cells, then determined its nucleotide sequence by the 5'-RACE method followed by confirmation employing the human genome DNA library. The isolated uridine/cytidine kinase cDNA (UCK cDNA) consisted of 786 nucleotides encoding 261 amino acids and was found to have approximately 70% homology with mouse UCK cDNA. Northern blot analysis of human leukemia RNAs with labeled UCK gene showed a single band at 1.6 kb to be UCK mRNA, and southern blot analysis of the UCK cDNA after digestion with BamHI, SacI and XbaI enzymes showed four band signals, suggesting the UCK gene to have at least 4 exons. A truncated form of UCK cDNA was expressed as the His-tag conjugated protein in Escherichia coli. The expressed and purified protein specifically converted uridine and cytidine to their corresponding monophosphates and also phosphorylated antitumor nucleosides such as 5-fluorouridine, cyclopentenyl-cytosine and 3'-C-ethynylcytidine. The present results suggest that our cloned human UCK cDNA encodes the correct amino acid sequence for UCK protein, showing high intracellular phosphorylation activity forward natural and synthetic pyrimidine nucleosides.
UI - 21398001
AU - Nishiguchi S; Shiomi S; Ofuji S; Ishizu H; Iwata Y; Sasaki N; Minamitani
TI - S; Ochi H Leiomyosarcoma of the liver detected by high F-18 fluorodeoxyglucose positron emission tomographic uptake.
SO - Clin Nucl Med 2001 Sep;26(9):798-9
AD - Third Department of Internal Medicine, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
UI - 21434723
AU - Wirbel RJ; Schulte M; Mutschler WE
TI - Surgical treatment of pelvic sarcomas: oncologic and functional outcome.
SO - Clin Orthop 2001 Sep;(390):190-205
AD - Department of Trauma Surgery, University of Saarland, Homburg, Germany.
The experiences in treating 93 consecutive patients (56 males, 37 females; mean age, 38.5 years; range, 4-69 years), including 76 patients with primary malignant bone tumors and 17 patients with soft tissue sarcomas involving the innominate bone, are reported. Oncologic and functional results were investigated in relation to the tumor stage, to the achieved surgical margin, and to the surgical procedure (hemipelvectomy, internal hemipelvectomy and endoprosthetic replacement, and continuity resection). The mean followup was 48 months (range, 8-222 months). The 5-year survival was 86% in patients with low-grade malignant bone tumors, 42% in patients with high-grade malignant bone tumors, and 25% in patients with high-grade soft tissue sarcomas. Survival was influenced by the grade of malignancy, the tumor stage, and the achieved surgical margins. Forty-six patients who survived were examined an average of 36 months after primary surgery. Excellent and good functional results were seen in 82% of patients who underwent continuity resection and in 55.5% of patients who underwent partial or total internal hemipelvectomy. All patients who survived hemipelvectomy had poor functional results. Surgical treatment of pelvic sarcomas is an extensive procedure with a considerable incidence of complications. It requires the knowledge of different techniques of resection and reconstruction of bone, joints, soft tissue, and intrapelvic organs.
UI - 21436366
AU - Challine D; Roudot-Thoraval F; Sarah T; Laperche L; Boisson B;
TI - Mauberquez S; Dubernet F; Rigot P; Lefrere F; Mercier B; Brossard Y; Rouet F; Girot R; Loiseau P; Girard D; Claquin J; Loty B; Lerable J; Mariotti M; Pawlotsky JM; Lefrere JJ Seroprevalence of human herpes virus 8 antibody in populations at high or low risk of transfusion, graft, or sexual transmission of viruses.
SO - Transfusion 2001 Sep;41(9):1120-5
AD - Bacteriology and Virology Laboratory, Henri Mondor Hospital, Paris XII University, Creteil, France.
BACKGROUND: The routes of transmission of human herpes virus 8 (HHV-8) remain unclear. In particular, HHV-8 transmission by blood components and organ transplantation is still debated and raises public health issues. The objective of this study was to determine the prevalence of anti-HHV-8 in selected populations of persons or patients with or without risk factors for the transmission of viral infections, in order to determine the routes of HHV-8 transmission. STUDY DESIGN AND METHODS: A total of 1431 persons or patients at low or high risk of sexually, blood-, or graft-transmitted viral infections were tested by means of a standardized immunofluorescence serologic assay detecting anti-HHV-8. RESULTS: The persons or patients could be classified into three distinct groups according to anti-HHV-8 prevalence: a low prevalence group (0.0% to 5.0%), including healthy blood donors, healthy pregnant women, multiply transfused patients with thalassemia major, and IV drug users; an intermediate prevalence group (5.0% to 20.0%), including organ donors, kidney transplant recipients, and multiply transfused patients with sickle cell disease; a high prevalence group (>20.0%), including HIV-negative persons at high risk of sexually-transmitted viral infections, and HIV-infected homosexual men and heterosexuals. CONCLUSION: The sexual route appears to be the main route of HHV-8 transmission; bloodborne transmission of HHV-8, if it exists, is rare. In contrast, organ transplantation recipients might be exposed to HHV-8 transmission by the transplanted organ, which raises the issue of systematic screening of organ donors.
UI - 21445657
AU - Meis-Kindblom JM; Sjogren H; Kindblom LG; Peydro-Mellquist A; Roijer E;
TI - Aman P; Stenman G Cytogenetic and molecular genetic analyses of liposarcoma and its soft tissue simulators: recognition of new variants and differential diagnosis.
SO - Virchows Arch 2001 Aug;439(2):141-51
AD - Department of Pathology and the Musculoskeletal Tumor Center, Goteborg University, Sahlgrenska University Hospital, Sweden. email@example.com
Liposarcoma is one of the most common sarcomas of adults. Its differential diagnosis and accurate subclassification are often problematic; the latter is also important with regard to appropriate treatment and prognosis. We studied a series of 23 liposarcomas that had unusual or previously undescribed features and 10 liposarcoma simulators and correlated the morphologic, cytogenetic, and molecular genetic findings. We found that use of cytogenetic-molecular genetic techniques aids in the distinction between myxoid-round cell liposarcoma and their simulators, chondroid lipoma, myxoid spindle cell-pleomorphic lipoma, cellular intramuscular myxoma, and myxofibrosarcoma. Poorly differentiated forms of round cell liposarcoma lacking morphologic evidence of lipogenesis can also be diagnosed using these techniques; however, the techniques do not aid in distinguishing low-grade myxoid from high-grade round cell liposarcomas. This study also shows that retroperitoneal liposarcomas with myxoid liposarcoma-like zones are part of the morphologic spectrum of well-differentiated-dedifferentiated liposarcoma rather than true myxoid liposarcomas. Perhaps most importantly, our results provide the first molecular genetic evidence that true mixed liposarcomas (mixed well-differentiated and myxoid liposarcoma) do indeed exist. They also unequivocally demonstrate the existence of small, round cell variants of pleomorphic liposarcoma that closely simulate myxoid-round cell liposarcoma.
UI - 21445658
AU - Nishio J; Iwasaki H; Ishiguro M; Ohjimi Y; Isayama T; Naito M; Kikuchi M
TI - Identification of syt-ssx fusion transcripts in both epithelial and spindle cell components of biphasic synovial sarcoma in small tissue samples isolated by membrane-based laser microdissection.
SO - Virchows Arch 2001 Aug;439(2):152-7
AD - Department of Pathology, School of Medicine, Fukuoka University, Japan.
In order to confirm the presence of SYT-SSX fusion gene in epithelial and spindle cell components of synovial sarcoma, we performed a nested reverse transcriptase-polymerase chain reaction (RT-PCR) using microbeam microdissection of membrane-mounted native tissue (MOMeNT) technique applied on formalin-fixed, paraffin-embedded tumor specimens from two biphasic synovial sarcomas and a control tissue of adamantinoma. Small targeted portions of either an epithelial or spindle cell component of the tumor tissue were microdissected together with the supporter membrane, by using an ultraviolet (337-nm) pulsed laser microbeam coupled into a robot-stage microscope with infinity optics. The SYT-SSX fusion transcript was detected in epithelial and spindle cell components of both biphasic synovial sarcomas, but not in the control tissue. Southern blot analysis also confirmed that the detected messages were derived from the SYT-SSX fusion gene. In conclusion, the microbeam MOMeNT is a useful method for isolating selected small portions from tissue sections. The SYT-SSX fusion gene is present in both cellular components of biphasic synovial sarcoma and is involved in oncogenesis of the synovial sarcoma rather than in morphologic epithelial differentiation. Therefore, in spite of the variable proportions of each component, our results confirm that the synovial sarcoma is of monoclonal origin.
UI - 21439146
AU - Li WW; Takahashi N; Jhanwar S; Cordon-Cardo C; Elisseyeff Y; Jimeno J;
TI - Faircloth G; Bertino JR Sensitivity of soft tissue sarcoma cell lines to chemotherapeutic agents: identification of ecteinascidin-743 as a potent cytotoxic agent.
SO - Clin Cancer Res 2001 Sep;7(9):2908-11
AD - Laboratories of Molecular Pharmacology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
The cytotoxic effects of ecteinascidin-743(ET-743), a novel marine natural product, were evaluated and compared with that of clinically used anticancer agents methotrexate, doxorubicin, etoposide, and paclitaxel in eight human soft tissue sarcoma (STS) cell lines. HT-1080, a fibrosarcoma cell line, and HS-42, a malignant mesodermal cell line, were the most sensitive of the cell lines to methotrexate, doxorubicin, etoposide, and paclitaxel. Other cell lines (IC50s) varied considerably and were more resistant to these agents. ET-743 was more potent than any of these agents, with IC50s in the pM range in all of the cell lines. Cytotoxicity of ET-743 was dose- and time-related (4-72 h exposure). Cytotoxic concentrations of ET-743 produced a S/G2 block in all of the cell lines tested. Three colon adenocarcinoma cell lines, HCT-8, HT-29, and HCT-116, and one breast cancer cell line, MCF-7, were 1-2 logs less sensitive to ET-743 than the STS cell lines. Cell lines were also characterized as to expression of oncogenes and tumor suppressor genes to attempt to correlate sensitivity of these cell lines to ET-743 and other chemotherapeutic agents. All of the cell lines except M8805, a malignant fibrous histiocytoma cell line, had mutations in p53 and/or overexpressed the MDM2 protein. Only HS-18, a liposarcoma cell line, lacked expression of the retinoblastoma protein. None of the cell lines had detectable expression of P-glycoprotein as measured by immunohistochemistry. ET-743 is an extremely potent cytotoxic agent against human STS cell lines and is being evaluated as an antitumor agent in this disease.
UI - 21441119
AU - Baillargeon J; Deng JH; Hettler E; Harrison C; Grady JJ; Korte LG;
TI - Alexander J; Montalvo E; Jenson HB; Gao SJ Seroprevalence of Kaposi's sarcoma-associated herpesvirus infection among blood donors from Texas.
SO - Ann Epidemiol 2001 Oct;11(7):512-8
AD - Department of Pediatrics, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
PURPOSE: Kaposi's sarcoma-associated herpesvirus (KSHV), a gammaherpesvirus recently discovered among AIDS patients with Kaposi's sarcoma, is a potential candidate for screening in blood and plasma donors. While a number of studies have assessed KSHV infection among U.S. blood donors, larger-scale population-based studies would be necessary to develop more refined estimates of the magnitude and variation of KSHV infection across different geographic regions of the U.S. blood supply. The goal of the present study, therefore, was to determine the seroprevalence of KSHV infection and to assess demographic correlates of KSHV infection among south Texas blood donors. METHODS: KSHV infection was determined using specific serologic assays that measure antibodies to KSHV latent and lytic antigens. RESULTS: The overall seroprevalence of KSHV in Texas blood donors (15.0%) is substantially higher than previously reported among blood donor and general population samples in the United States. This high rate of KSHV infection persisted across most of the sociodemographic subgroups under study but was particularly elevated among participants with less than a high school education. The infection rate also increased linearly with age. CONCLUSIONS: The elevated infection rate reported in the present study suggests that screening methods to detect KSHV infection in blood donors should be considered. In view of the etiologic role of KSHV for several malignancies, it would be important for future studies to directly assess the risk of KSHV transmission via blood transfusion.
UI - 21455251
AU - Gaumann A; Tews DS; Mayer E; Dahm M; Petrow PK; Otto M; James C;
TI - Kriegsmann J Expression of apoptosis-related proteins, p53, and DNA fragmentation in sarcomas of the pulmonary artery.
SO - Cancer 2001 Sep 1;92(5):1237-44
AD - Institute of Pathology, University of Mainz, Mainz, Germany. a.gaumann@Kerckhoff.mpg.de
BACKGROUND: Apoptosis is a common feature in a variety of pathologic conditions. Induction of apoptosis through apoptotic stimuli such as, chemotherapy or radiation, presents new insights into tumor biology and therapy. In particular, members of the Bcl-2 family as well as the Fas system are known to be involved in the regulation of apoptosis in different tumor entities. METHODS: In the current study, the expression of the apoptosis-related molecules p53, Bax, Bcl-2, Fas (CD95), Fas-Ligand and perforin was examined in 7 patients with a sarcoma of the pulmonary artery. Furthermore, the TUNEL-method for the detection of apoptotic cells was applied as well as sequencing of the p53 gene. RESULTS: In the TUNEL assay, approximately 10% of the sarcoma cells displayed DNA fragmentation. In addition, Bax was expressed in tumor cells. Accumulation of p53 was evident in 4 of 7 patients (pAB 240 antibody), and 2 of them were positive for the pAB 1801 antibody. Only 1 case had a point mutation in Exon 5 of the p53 sequence. A few tumor cells showed a double labeling of Bax and p53. Bcl-2 could be detected only in tumor-associated lymphocytes. Finally, several lymphocytes could be stained with perforin, but none of the specimens showed a reactivity for Fas or Fas-Ligand. CONCLUSION: The expression of Bax indicated a possible role of this molecule in programmed cell death in pulmonary sarcomas. The limited coexpression of Bax and p53 suggested that induction of Bax can occur independently of p53. The detection of perforin in lymphocytes suggested a possible role for this molecule in apoptosis of the sarcoma cells. In contrast, the Fas system did not seem to play an essential role in sarcomas of the great vessels. Copyright 2001 American Cancer Society.
UI - 21455264
AU - Patel SR; Jenkins J; Papadopolous N; Burgess MA; Plager C; Gutterman J;
TI - Benjamin RS Pilot study of vitaxin--an angiogenesis inhibitor-in patients with advanced leiomyosarcomas.
SO - Cancer 2001 Sep 1;92(5):1347-8
AD - Department of Sarcoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. firstname.lastname@example.org
UI - 21284295
AU - Vanel D; De Paolis M; Monti C; Mercuri M; Picci P
TI - Radiological features of 24 periosteal chondrosarcomas.
SO - Skeletal Radiol 2001 Apr;30(4):208-12
AD - Laboratorio di Ricerca Oncologica, Istituto Rizzoli, Bologna, Italy.
OBJECTIVE: To report the imaging findings of 24 periosteal chondrosarcomas diagnosed, staged, treated and followed in a single institution, to analyze and define their pattern, and discuss their practical consequences. DESIGN AND PATIENTS: Plain films, 16 CT examinations and four MRI examinations were reviewed, and compared with the histological evaluation. RESULTS: There were 20 men and four women, aged from 17 to 65 years. Twelve lesions involved the distal femoral metaphyses (8 posteriorly), five the proximal humerus, two the proximal metaphyses of the femur and two of the tibia, two the humeral shafts and one the iliac wing. Size varied from 4 to 11 cm. The cortex was always involved (thick, 15; thin, 13). Typical cartilaginous calcifications and cartilaginous lobules were very frequent. Radial thick periosteal bone formations (n = 6) indicated calcifications between the lobules of cartilage. Medullary involvement was rare (n = 2). All patients are alive and free of disease. CONCLUSIONS: Recognizing periosteal chondrosarcoma is of paramount importance because the prognosis is excellent after adequate local surgery alone. The patterns of other surface tumors of bone are usually different.
UI - 21453547
AU - Loos BM; Wieneke JA; Thompson LD
TI - Laryngeal angiosarcoma: a clinicopathologic study of five cases with a review of the literature.
SO - Laryngoscope 2001 Jul;111(7):1197-202
AD - Department of Otolaryngology-Head and Neck Surgery, Georgetown University Medical Center, Washington, DC, USA.
OBJECTIVE: Primary laryngeal angiosarcoma (LA) is rare without a reported series evaluating these tumors. STUDY DESIGN/METHODS: Five patients with LA were retrospectively retrieved from the Otorhinolaryngic Registry of the Armed Forces Institute of Pathology. RESULTS: Three men and 2 women, aged 29 to 71 years, presented with hoarseness (n = 4) and hemoptysis (n = 1). Two patients had previous neck radiation. The tumors involved the supraglottis (n = 4) with a mean size of 3.1 cm. Histologically, all tumors had anastomosing vascular channels lined by remarkably atypical endothelial cells protruding into the lumen, frequent atypical mitotic figures, and hemorrhage. All cases tested (n = 4) demonstrated immunoreactivity with antibodies to Factor VIII-RA and CD34. All patients had surgery followed by postoperative radiation (n = 3 patients). Three patients died with disease (mean, 17 mo), whereas one patient is alive with no evidence of disease at 18 years. CONCLUSIONS: LA is a rare tumor, frequently associated with previous radiation, usually involving the supraglottis with characteristic histomorphologic and immunophenotypic features. LA has a poor prognosis, making appropriate separation from other conditions important.
UI - 21390914
AU - Zhang Q; Yang Z; Bu G
TI - [Surgery of advanced clival tumors]
SO - Zhonghua Er Bi Yan Hou Ke Za Zhi 1998 Feb;33(1):21-3
AD - Third Teaching Hospital, Bethune University of Medical Sciences, Changchun 130031.
OBJECTIVE: To investigate the effects of surgical procedures on tumor 27 patients with advanced clival tumors during the last 9 years. METHODS: Four different kinds of surgical approaches were selected and used according to preoperative clinical and radiographic findings, and the complications and the long-term survival rates were evaluated after the surgical procedures. RESULTS: All of the 8 patients with benign clival tumors (6 cases with chordomas and 2 with meningiomas) had over 2-8 years survival and no severe complications after the surgical procedures and adjuvant radiotherapy. Fourteen of the 19 patients with malignant tumors had over 2-6 years survival (a survival rate of 73.7%) after the surgical procedures, the adjuvant chemotherapy and radiotherapy. CONCLUSION: Surgery of the clivus appears to be worthwhile procedure for improving outcome of the patients with advanced clival tumors.
UI - 21418712
AU - Cunha A; Costa SC; Lima CS; Ortega M; Costa FF
TI - Low incidence of human herpesvirus 8 in bone marrow samples from Brazilian patients with multiple myeloma.
SO - Acta Haematol 2001;105(4):247-8
AD - Department of Internal Medicine and Department of Clinical Pathology, University of Campinas (UNICAMP), CEP Campinas, SP, 13083-970, Brazil.
UI - 21423990
AU - Katz RA; DiCandeloro P; Kukolj G; Skalka AM
TI - Role of DNA end distortion in catalysis by avian sarcoma virus integrase.
SO - J Biol Chem 2001 Sep 7;276(36):34213-20
AD - Fox Chase Cancer Center, Institute for Cancer Research, Philadelphia, Pennsylvania 19111, USA. R_Katz@fccc.edu
Retroviral integrase (IN) recognizes linear viral DNA ends and introduces nicks adjacent to a highly conserved CA dinucleotide usually located two base pairs from the 3'-ends of viral DNA (the "processing" reaction). In a second step, the same IN active site catalyzes the insertion of these ends into host DNA (the "joining" reaction). Both DNA sequence and DNA structure contribute to specific recognition of viral DNA ends by IN. Here we used potassium permanganate modification to show that the avian sarcoma virus IN catalytic domain is able to distort viral DNA ends in vitro. This distortion activity is consistent with both unpairing and unstacking of the three terminal base pairs, including the processing site adjacent to the conserved CA. Furthermore, the introduction of mismatch mutations that destabilize the viral DNA ends were found to stimulate the IN processing reaction as well as IN-mediated distortion. End-distortion activity was also observed with mutant or heterologous DNA substrates. However, further analyses showed that using Mn(2+) as a cofactor, processing site specificity of these substrates was also maintained. Our results support a model whereby unpairing and unstacking of the terminal base pairs is a required step in the processing reaction. Furthermore, these results are consistent with our previous observations indicating that unpairing of target DNA promotes the joining reaction.
UI - 21424528
AU - Groves AK; Cotter MA; Subramanian C; Robertson ES
TI - The latency-associated nuclear antigen encoded by Kaposi's sarcoma-associated herpesvirus activates two major essential Epstein-Barr virus latent promoters.
SO - J Virol 2001 Oct;75(19):9446-57
AD - Medical Scientist Training Program, Cell and Molecular Biology Graduate Program, Department of Microbiology and Immunology, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0934, USA.
The latency-associated nuclear antigen (LANA) encoded by the Kaposi's sarcoma-associated herpesvirus (KSHV) is expressed in the majority of KSHV-infected cells and in cells coinfected with Epstein-Barr virus (EBV). In coinfected body cavity-based lymphomas (BCBLs), EBV latent membrane protein 1 (LMP1), which is essential for B-lymphocyte transformation, is expressed. EBNA2 upregulates the expression of LMP1 and other cellular genes through specific interactions with cellular transcription factors tethering EBNA2 to its responsive promoters. In coinfected BCBL cells, EBNA2 is not detected but LANA, which is constitutively expressed, contains motifs suggestive of potential transcriptional activity. Additionally, recent studies have shown that LANA is capable of activating cellular promoters. Therefore, we investigated whether LANA can affect transcription from two major EBV latent promoters. In this study, we demonstrated that LANA can efficiently transactivate both the LMP1 and C promoters in the human B-cell line BJAB as well as in the human embryonic kidney 293 cell line. Moreover, we demonstrated that specific domains of LANA containing the putative leucine zipper and the glutamic acid-rich region are highly effective in upregulating these viral promoters, while the amino-terminal region (435 amino acids) exhibited little or no transactivation activity in our assays. We also specifically tested truncations of the LMP1 promoter element and showed that the -204 to +40 region had increased levels of activation compared with a larger region, -512 to +40, which contains two recombination signal-binding protein J kappa binding sites. The smaller, -204 to +40 promoter region contains specific binding sites for the Ets family transcription factor PU.1, transcription activating factor/cyclic AMP response element, and Sp1, all of which are known to function as activators of transcription. Our data therefore suggest a potential role for LANA in regulation of the major EBV latent promoters in KSHV- and EBV-coinfected cells. Furthermore, LANA may be able to activate transcription of viral and cellular promoters in the absence of EBNA2, potentially through association with transcription factors bound to their cognate sequences within the -204 to +40 region. This regulation of viral gene expression is critical for persistence of these DNA tumor viruses and most likely involved in mediating the oncogenic process in these coinfected cells.
UI - 21424534
AU - Hwang S; Gwack Y; Byun H; Lim C; Choe J
TI - The Kaposi's sarcoma-associated herpesvirus K8 protein interacts with CREB-binding protein (CBP) and represses CBP-mediated transcription.
SO - J Virol 2001 Oct;75(19):9509-16
AD - Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame K8 encodes a basic region-leucine zipper protein of 237 amino acids that homodimerizes with its bZIP domain. KSHV K8 shows significant homology to the Epstein-Barr virus (EBV) immediate-early protein Zta, a key regulator in the reactivation and replication of EBV. In this study, we report that K8, like its homolog EBV Zta, interacts with cellular CREB-binding protein (CBP) in vivo and in vitro. This interaction requires the C/H3 domain of CBP and the basic region of K8. K8 represses CBP-mediated transcription by competing with limited amounts of cellular CBP, exemplified by the reduced expression from the AP-1 and human immunodeficiency virus long terminal repeat promoters.
UI - 21424854
AU - Graham D
TI - Management of soft tissue sarcoma.
SO - Nurs Clin North Am 2001 Sep;36(3):553-65, xi
AD - Advanced Practice, Education and Research, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. email@example.com
Sarcomas are rare and unusual neoplasms that can be found in any tissue and can have life-threatening outcomes. Caring for these patients can be a great challenge and requires a multidisciplinary team.
UI - 21433392
AU - Zietz C; Rumpler U; Sturzl M; Lohrs U
TI - Inverse relation of Fas-ligand and tumor-infiltrating lymphocytes in angiosarcoma: indications of apoptotic tumor counterattack.
SO - Am J Pathol 2001 Sep;159(3):963-70
AD - Institute of Pathology, Ludwig Maximilians University, Munich, Germany. firstname.lastname@example.org
Fas and Fas-L regulate immune responses through the induction of cell death. Fas-L is commonly expressed in activated immune cells and in the endothelium. In the latter it contributes to the inhibition of transvascular cell migration by the induction of apoptosis in Fas-bearing lymphocytes. Here we investigated whether the Fas/Fas-L system may regulate lymphocyte invasion into angiosarcomas. Fas and Fas-L expression was quantitatively determined in different grade angiosarcomas (n = 40) and related to the number of extravasated tumor-infiltrating lymphocytes (TILs). Fas expression was detected in < 50% of the cases. In positive tumors both the number of Fas-positive cells and the staining intensity were highly variable and did not correlate with the number of TILs, the mean time of survival, and the histopathological tumor grade. By contrast, Fas-L expression was detected in >70% of the cases and the relative numbers of Fas-L-positive cells correlated inversely with the numbers of CD3- and CD8-positive TILs (P < or = 0.004). The survival times of patients with high Fas-L-expressing angiosarcomas were significantly reduced as compared to patients with low Fas-L-expressing tumors. Our results show that angiosarcomas with low Fas-L expression are characterized by numerous TILs, whereas sarcomas with high Fas-L expression show significantly reduced numbers of TILs. These results suggest that the Fas/Fas-L system may repress TIL invasion into angiosarcoma and by this may contribute to the evasion of the anti-tumor immune surveillance of angiosarcoma in the course of an apoptotic tumor counterattack mechanism.
UI - 21443303
AU - Worley BS; van den Broeke LT; Goletz TJ; Pendleton CD; Daschbach EM;
TI - Thomas EK; Marincola FM; Helman LJ; Berzofsky JA Antigenicity of fusion proteins from sarcoma-associated chromosomal translocations.
SO - Cancer Res 2001 Sep 15;61(18):6868-75
AD - Metabolism Branch, National Cancer Institute, Bethesda, Maryland 20892-1578, USA.
Synovial sarcoma (SS), clear cell sarcoma (CCS), and desmoplastic small round cell tumor (DSRCT) are soft-tissue malignancies occurring primarily in adolescents and young adults. These tumors contain specific chromosomal translocations that fuse the 5' region of one gene with the 3' region of another, resulting in the formation of characteristic fusion proteins. These translocations are unique to tumor cells and may be required for persistence, thereby serving as targets for immunotherapy. It was hypothesized that the fusion breakpoint sequences associated with SS, CCS, and DSRCT can serve as tumor-specific neoantigens. To test this, peptides corresponding to the fusion breakpoints were designed and assessed for ability to bind to various class I HLA molecules. Two peptides derived from the SS breakpoint specifically bind the HLA-B7 antigen, and a 10-amino acid minimal epitope was identified for this interaction. Specific binding of a SS peptide and a CCS peptide to HLA-B27 molecule was also observed. Finally, a peptide designed from the DSRCT breakpoint specifically binds the HLA-A3 molecule, and a 9-amino acid optimal epitope was identified for this interaction. The physiological/immunological relevance of these peptide/MHC interactions was demonstrated by the induction of SS-specific CTLs from normal donor lymphocytes using in vitro stimulation with autologous, peptide-pulsed dendritic cells and by the ability of these CTLs to lyse human SS tumor cells endogenously expressing the full-length fusion protein. These results suggest that sequences in the fusion region of sarcoma-associated chimeras can bind class I HLA molecules and serve as neoantigens. These may be useful for the development of novel immunotherapies for sarcoma patients with appropriate HLA molecules and tumors bearing these translocations.
UI - 21453163
AU - Callister MD; Ballo MT; Pisters PW; Patel SR; Feig BW; Pollock RE;
TI - Benjamin RS; Zagars GK Epithelioid sarcoma: results of conservative surgery and radiotherapy.
SO - Int J Radiat Oncol Biol Phys 2001 Oct 1;51(2):384-91
AD - Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
PURPOSE: To determine the outcome and prognostic factors for patients with localized epithelioid sarcoma treated with conservative surgery and radiotherapy (RT). METHODS AND MATERIALS: The medical records of 24 patients with nonmetastatic epithelioid sarcoma treated with conservative surgery and RT were reviewed. Preoperative RT was given to 3 patients (median 46.4 Gy) and postoperative RT to 21 patients (median 64.5 Gy). A local (limb-sparing) surgical procedure was performed in all patients. RESULTS: At a median follow-up of 131 months, 14 patients had relapsed and 13 patients had died. The actuarial overall and disease-free survival rate at 10 years was 50% and 37%, respectively. Local, nodal, and metastatic failure occurred in 7, 4, and 10 patients, respectively, yielding a 10-year actuarial local, nodal, and metastatic control rate of 63%, 81%, and 56%, respectively. Univariate analysis revealed that size < or =5 cm and extremity location were favorable prognostic factors for overall, disease-free, and metastasis-free survival. The actuarial 5-year overall, disease-free, and metastasis-free survival rate was 79% vs. 25% (p = 0.002), 51% vs. 13% (p = 0.03), and 79% vs. 13% (p <0.001), respectively, for lesion size < or =5 vs. > 5 cm. The actuarial 5-year overall, disease-free, and metastasis-free survival rate was 77% vs. 39% (p = 0.002), 56% vs. 0% (p = 0.01), and 78% vs. 17% (p = 0.01), respectively, for extremity vs. nonextremity location. Multivariate analysis of the factors correlating with the overall, disease-free, and metastasis-free survival confirmed the favorable prognostic significance of small lesion size. The prognostic significance of extremity location on univariate analysis was explained by an imbalance in the mean tumor sizes. CONCLUSIONS: Epithelioid sarcoma is an aggressive soft-tissue sarcoma, with high rates of local and distant relapse. Local control with conservative surgery and RT compares favorably to published surgical series. The poor outcome for tumors > or =5 cm in size emphasizes the need for effective systemic therapy.
UI - 21453164
AU - Noel G; Habrand JL; Mammar H; Pontvert D; Haie-Meder C; Hasboun D;
TI - Moisson P; Ferrand R; Beaudre A; Boisserie G; Gaboriaud G; Mazal A; Kerody K; Schlienger M; Mazeron JJ Combination of photon and proton radiation therapy for chordomas and chondrosarcomas of the skull base: the Centre de Protontherapie D'Orsay experience.
SO - Int J Radiat Oncol Biol Phys 2001 Oct 1;51(2):392-8
AD - Centre de Protontherapie d'Orsay, Orsay, France. email@example.com
PURPOSE: Prospective analysis of local tumor control, survival, and treatment complications in 44 consecutive patients treated with fractionated photon and proton radiation for a chordoma or chondrosarcoma of the skull base. METHODS AND MATERIALS : Between years (14-85) were treated using a 201-MeV proton beam at the Centre de Protontherapie d'Orsay, 34 for a chordoma and 11 for a chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented two-thirds of the total dose and protons one-third. The median total dose delivered within the gross tumor volume was 67 cobalt Gray equivalent (CGE) (range: 60-70). RESULTS: With a mean follow-up of 30.5 months (range: 2-56), the 3-year local control rates for chordomas and chondrosarcomas were 83.1% and 90%, respectively, and 3-year overall survival rates were 91% and 90%, respectively. Eight patients (18%) failed locally (7 within the clinical tumor volume and 1 unknown). Four patients died of tumor and 2 others of intercurrent disease. In univariate ana