National Cancer Institute®
Last Modified: September 1, 2002
UI - 11856592
AU - Reichardt P
TI - High-dose chemotherapy in adult soft tissue sarcoma.
SO - Crit Rev Oncol Hematol 2002 Feb;41(2):157-67
AD - Medizinische Klinik m. S. Hamatologie, Onkologie und Tumorimmunologie, Robert-Rossle-Klinik, Universitatsklinikum Charite der Humboldt-Universitat zu Berlin, 13122, Berlin, Germany. email@example.com
Soft tissue sarcomas represent a rare and heterogeneous disease. Only few drugs have been identified to be active, with doxorubicin, epirubicin and ifosfamide being the only agents with response rates above 20%. Combination chemotherapy results in higher response rates, however, superiority against single agent chemotherapy in terms of survival has not been established yet. Since a dose-response relationship is suggested for the anthracyclines and especially ifosfamide, high-dose or dose-intensive chemotherapy with bone marrow or stem cell support has been evaluated by several investigators. The studies are usually small, and included a very heterogeneous group of patients. Randomized trials have not been done, so that definite conclusions cannot be drawn to date. High-dose chemotherapy in soft tissue sarcoma has to be considered highly investigational and should not be performed outside clinical trials. Future studies should be focused on the development of active regimens, resulting in complete remission rates, that can be expected to translate into longer survival. Finally, well designed and appropriately powered randomized trials, using established prognostic and predictive factors, should be carried out, preferably in younger patients and in the context of a potentially curative multimodality approach.
UI - 11856594
AU - Atra A; Pinkerton R
TI - High-dose chemotherapy in soft tissue sarcoma in children.
SO - Crit Rev Oncol Hematol 2002 Feb;41(2):191-6
AD - Department of Paediatric Oncology, The Royal Marsden Hospital NHS Trust/Institute of Cancer Research, Downs Road, Sutton, SM2 5PT, Surrey, UK.
Soft tissue sarcomas (STS) are highly malignant tumours that constitute 5-6% of all malignant childhood neoplasms. Of these, rhabdomyosarcoma (RMS) is the most common in children, and has a characteristic two-peak age incidence, 2-5 and 15-19 years. Most children with RMS are cured with conventional chemotherapy and local therapy (surgery with or without radiotherapy). Children with metastatic disease at presentation, particularly those older than 10 years or with bone marrow or bone involvement have a much poorer outcome. In this subgroup, high-dose therapy with stem cell rescue has been studied over the last two decades. Various single or multiagent chemotherapy regimens with or without radiotherapy and autologous stem cell rescue have been used as consolidation treatment with little success. Recent trials using sequential high-dose chemotherapy in the early phase of treatment have proved to be feasible, but the beneficial effect has to be confirmed. The role of purging remains unclear. Collaboration between different international groups is urgently required, in an attempt to improve the poor outcome of children with high risk STS.
UI - 12044238
AU - Raney RB
TI - Soft-tissue sarcoma in childhood and adolescence.
SO - Curr Oncol Rep 2002 Jul;4(4):291-8
AD - Division of Pediatrics, University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 87, Houston 77030, USA. Braney@mdanderson.org
This review summarizes and comments on the major articles that have been published in English concerning pediatric soft-tissue sarcomas in the past 2 years. Studies of rhabdomyosarcoma and undifferentiated sarcoma, including late sequelae of treatment; nonrhabdomyosarcomatous soft-tissue sarcoma; and the pathology of soft-tissue sarcomas are included.
UI - 12044239
AU - Patel SR
TI - Systemic therapy for advanced soft-tissue sarcomas.
SO - Curr Oncol Rep 2002 Jul;4(4):299-304
AD - Department of Sarcoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 450, Houston 77030, USA. firstname.lastname@example.org
The field of oncology is experiencing a paradigm shift from broad-spectrum cytotoxic therapies to more specific molecularly based targeted therapies. The activity of imatinib mesylate in chronic myelogenous leukemia and gastrointestinal stromal tumors (GIST) has reinforced our faith in translational research and its potential impact on the cure of cancer and improvement in quality of life for patients. This breakthrough has been particularly exciting for the field of sarcoma and for patients with advanced GIST, for whom no other effective therapy was available. Unfortunately, as is becoming increasingly clear, cancer is a very complex problem with multiple mechanisms and pathways that function either independently or interdependently enabling cell survival. We are therefore far away from having solved the problem. Attempts at refining the currently available therapeutic armamentarium to maximize the therapeutic index (dose intensification with growth factor support) must continue in parallel with laboratory-based research identifying critical targets to be inhibited or blocked. Identification of new agents with some activity, such as gemcitabine and ecteinascidin (ET-743), is also of paramount importance.
UI - 12075208
AU - Al-Khateeb T; Bataineh AB
TI - Rhabdomyosarcoma of the oral and maxillofacial region in Jordanians: a retrospective analysis.
SO - Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002 May;93(5):580-5
AD - Jordan University of Science and Technology. Irbid, Jordan. Khateeb@just.edu.jo
OBJECTIVE: The objective was to study the clinicopathologic features of rhabdomyosarcoma (RMS) of the oral and maxillofacial region in Jordanians. STUDY DESIGN: Data were collected from records of patients treated between 1989 and 2000 at the Maxillofacial Unit of Jordan University of Science and Technology. The main outcome measures were age, gender, location, stage of disease, histopathologic type, treatment received, follow-up period, and eventual outcome. RESULTS: Nine patients with RMS aged 4 to 17 years were found, with a male to female ratio of 2:1. Six (67%) bony sites and 7 (78%) soft tissue sites were involved. The extent of disease was locoregional in 8 (89%) cases, nodal in 3 (33%) cases, and distant metastatic in 2 (22%) cases. The Intergroup Rhabdomyosarcoma Study classification of clinical groups was as follows: 2 (22%) cases in stage II, 5 (56%) cases in stage III, and 2 (22%) cases in stage IV. The histopathologic types found were 6 (67%) embryonal, 2 (22%) alveolar, and 1 (11%) undifferentiated. Triple agent chemotherapy was used in the treatment of 8 cases, singly or in combination with surgery or radiotherapy. Two patients are still alive, and 5 patients have died of disease. CONCLUSIONS: The clinicopathologic features of maxillofacial RMS in this group of Jordanians are different from those of people from other countries. Further studies are needed to have a better understanding of the behavior of RMS in the oral and maxillofacial area.
UI - 12187831
AU - Suzuki A
TI - [Enhanced expression of matrix metalloproteinase-9 (MMP-9) under hypoxic and nutrient-deprived conditions]
SO - Hokkaido Igaku Zasshi 2002 Jul;77(4):351-7
AD - Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
UI - 11999659
AU - Rhee MY; Myong NH; Park YB
TI - Primary intimal sarcoma of the aorta: role of transesophageal echocardiography.
SO - Circ J 2002 Jan;66(1):111-3
AD - Department of Internal Medicine, College of Medicine, Dankook University, Cheonan, Choongnam, Korea. email@example.com
Diagnosis of primary tumors of the aorta is difficult. A patient who had a primary intimal sarcoma of the aorta with metastasis presented with obstructive symptoms and computed tomography showed a thrombus-like mass in the aorta. However, transesophageal echocardiography revealed an inhomogeneous and echo-dense mass with an outer membrane, unlike a thrombus, and suggestive of a primary aortic tumor. Pathologic examination of specimens from exploration and autopsy revealed a primary intimal sarcoma.
UI - 12010367
AU - Lopes JM; Nesland JM; Reis-Filho JS; Holm R
TI - Differential Ki67 and bcl-2 immunoexpression in solid-glandular and spindle cell components of biphasic synovial sarcoma: a double immunostaining assessment with cytokeratin and vimentin.
SO - Histopathology 2002 May;40(5):464-71
AD - Institute of Molecular Pathology and Immunology (IPATIMUP) and Porto Medical School, University of Porto, Porto, Portugal.
AIMS: Synovial sarcoma is a malignant soft tissue of uncertain histogenesis that may show a biphasic (spindle and solid/glandular components) or a monophasic histological appearance. In previous studies, we demonstrated that the solid/glandular component possesses higher proliferation rates than the spindle cell component of biphasic synovial sarcomas and that the spindle cell component may exhibit a progressive transition from or to the solid-glandular component in biphasic synovial sarcoma. To evaluate this hypothesis further, we designed a novel approach to correlate immunoexpression of Ki67, bcl-2 and bax in the spindle cell and in the solid-glandular component of biphasic synovial sarcomas. We also performed a double-immunohistochemical assessment of the Ki67 proliferative indices and the immunoexpression of anti-apoptotic protein bcl-2 in neoplastic cells expressing either vimentin or cytokeratin. METHODS AND RESULTS: Immunohistochemistry for vimentin (10 cases), bcl-2 (10 cases), Ki67(10 cases), cytokeratin (10 cases), and bax (eight cases), and double-immunostaining for vimentin/Ki67 (10 cases), vimentin/bcl-2 (nine cases), cytokeratin/Ki67 (10 cases), and cytokeratin/bcl-2 (10 cases) assays were performed in 10 cases of primary biphasic synovial sarcoma. Semiquantitative assessment was adopted for each case in both components. Statistical analysis was performed using Fisher's exact test or chi2 test. On conventional immunohistochemistry, the solid/glandular component revealed more expression of Ki67, bax and cytokeratin than the spindle cell component (P=0.0004, P=0.082, and P < 0.0001, respectively); on the other hand, the latter showed higher expression of bcl-2 and vimentin than the former (P=0.0281 and P=0.059, respectively). Double immunohistochemistry analysis revealed higher co-expression levels of cytokeratin/Ki67 and cytokeratin/bcl-2 than the spindle cell component (P=0.015 and P < 0.0001, respectively); conversely, the latter presented higher co-expression of vimentin/bcl-2 than the former (P=0.0007). All cases showed no more than 10% of cells coexpressing cytokeratin/bcl-2, cytokeratin/Ki67, and no case revealed cells coexpressing vimentin/Ki67. CONCLUSION: Our findings indicate that in biphasic synovial sarcoma the acquisition of epithelial phenotype (solid/glandular component) is associated with a high expression of pro-apoptotic proteins and a high proliferative differentiation status, and conversely, mesenchymal phenotype (spindle cell component) is associated with a high expression of apoptosis-inhibitor bcl-2 and a low proliferative terminal-type differentiation status.
UI - 12149295
AU - Spunt SL; Hill DA; Motosue AM; Billups CA; Cain AM; Rao BN; Pratt CB;
TI - Merchant TE; Pappo AS Clinical features and outcome of initially unresected nonmetastatic pediatric nonrhabdomyosarcoma soft tissue sarcoma.
SO - J Clin Oncol 2002 Aug 1;20(15):3225-35
AD - Department of Hematology-Oncology, St Jude Children's Research Hospital, University of Tennessee College of Medicine, 332 N. Lauderdale Street, Memphis, TN 38105-2794, USA. firstname.lastname@example.org
PURPOSE: To describe the clinical features, response to therapy, and outcome of pediatric patients with initially unresected nonmetastatic nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). PATIENTS AND METHODS: We retrospectively reviewed the presenting clinical features and tumor characteristics of all 40 pediatric patients with initially unresected information was available was analyzed to determine whether response to therapy was associated with local disease control and event-free and overall survival. RESULTS: More than 70% of the 40 patients had tumors with high-risk features (tumor size > 5 cm, high grade, invasiveness). For the 27 patients included in the outcome analysis, 5-year event-free survival and survival estimates were 33% +/- 9% and 56% +/- 10%, respectively. Ten (37%) of these patients had a complete or partial response to neoadjuvant chemotherapy and/or radiotherapy, and only two of the 10 had residual tumor after surgery. Combined chemotherapy and radiotherapy seemed more effective than either modality alone in inducing a response, but the response to neoadjuvant therapy did not predict outcome. Most treatment failures were local, and postrelapse survival was poor (19% +/- 10%). CONCLUSION: Initially unresected NRSTS constitutes a unique subgroup of pediatric sarcomas that commonly present with high-risk features and respond poorly to neoadjuvant therapy. Only about one third of patients treated with multimodal therapy remain disease-free, and local control is the major limiting factor in achieving cure. More effective risk-directed treatments are needed for this unique subgroup of patients.
UI - 12149303
AU - Stein U; Jurchott K; Schlafke M; Hohenberger P
TI - Expression of multidrug resistance genes MVP, MDR1, and MRP1 determined sequentially before, during, and after hyperthermic isolated limb perfusion of soft tissue sarcoma and melanoma patients.
SO - J Clin Oncol 2002 Aug 1;20(15):3282-92
AD - Division of Surgery and Surgical Oncology, Charite, Humboldt University, Campus Berlin-Buch, Robert Rossle Hospital and Tumor Institute, Robert-Rossle-Strasse 10, 13092 Berlin, Germany. email@example.com
PURPOSE: Isolated, hyperthermic limb perfusion (ILP) with recombinant human tumor necrosis factor alpha and melphalan is a highly effective treatment for advanced soft tissue sarcoma (STS) and locoregional metastatic malignant melanoma. Multidrug resistance (MDR)-associated genes are known to be inducible by heat and drugs; expression levels of the major vault protein (MVP), MDR1, and MDR-associated protein 1 (MRP1) were determined sequentially before, during, and after ILP of patients. PATIENTS AND METHODS: Twenty-one STS or malignant melanoma patients were treated by ILP. Tumor tissue temperatures were recorded continuously and ranged from 33.4 degrees C initially to peak values of 40.4 degrees C during ILP. Serial true-cut biopsy specimens from tumor tissues were routinely microdissected. Expression analyses for MDR genes were performed by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. RESULTS: In 83% of the patients, MVP expression was induced during hyperthermic ILP. MVP-mRNA inductions often paralleled the increase in temperature during ILP. Increased MVP protein expressions either were observed simultaneously with the MVP-mRNA induction or were delayed until after the induction at the transcriptional level. Inductions of MDR1 and MRP1 were observed in only 13% and 27% of the specimens analyzed. Temperatures and drugs applied preferentially led to an induction of MVP and were not sufficient to induce MDR1 and MRP1 in the majority of tumors. CONCLUSION: This study is the first to analyze the expression of MDR-associated genes sequentially during ILP of patients and demonstrates that treatment might lead to increased levels of MVP, whereas enhanced levels of MDR1 and MRP1 remain rare events.
UI - 9789611
AU - Leyvraz S; Bacchi M; Cerny T; Lissoni A; Sessa C; Bressoud A; Hermann R
TI - Phase I multicenter study of combined high-dose ifosfamide and doxorubicin in the treatment of advanced sarcomas. Swiss Group for Clinical Research (SAKK).
SO - Ann Oncol 1998 Aug;9(8):877-84
AD - Serge.Leyvraz@chuv.hospvd.ch
Ifosfamide and doxorubicin are the most active agents in the treatment of sarcomas and are characterized by a marked dose-response relationship. The objective of this study was to determine the maximum tolerated dose (MTD) of both agents in combination under granulocyte-macrophage colony-stimulating factor (GM-CSF) cover. PATIENTS AND METHODS: Thirty-three patients with untreated sarcomas (soft tissue: n = 20; gynecological: n = 11; bone: n = 2) were treated with ifosfamide 12 g/m2 by continuous i.v. infusion over five days and doxorubicin with dose escalation from 50 mg/m2 i.v. bolus divided on two days, then to 60 mg/m2 bolus divided on three days. Ifosfamide was reduced to 10 g/m2 and doxorubicin was further escalated up to 90 mg/m2. GM-CSF (5 micrograms/kg/day subcutaneously) was started 24 hours after chemotherapy and continued for 10 days. RESULTS: The MTD was reached with the combination of ifosfamide at 12 g/m2 and doxorubicin at 60 mg/m2. But with ifosfamide 10 g/m2 and doxorubicin 90 mg/m2 the MTD was not obtained. While severe leukopenia and granulopenia were observed at all-dose levels, severe anemia was more frequently related to the highest dose of ifosfamide. Severe thrombopenia and mucositis were more commonly observed at the highest dose of doxorubicin. Ifosfamide 10 g/m2 and doxorubicin 90 mg/m2 induced WHO grade 4 leukopenia in 58%, grade 3-4 thrombopenia in 42%, and anemia in 31% of cycles. Mucositis was minor in 50% of cycles. The overall response rate among 31 evaluable patients was 55% (95 confidence interval (CI): 36%-73%), with four (13%) complete responders and 13 (42%) partial responders. Response rates based on soft-tissue sarcomas or gynecological sarcomas alone were similar. Ten patients could be treated by elective surgery and/or radiotherapy. The total group of patients reached a median survival of two years, with 25% (SE 8%) survivors after three years. CONCLUSIONS: The dose level of ifosfamide 10 g/m2 and doxorubicin 90 mg/m2 with supportive GM-CSF is manageable in a multicenter setting and should be further tested in regular phase II trials, including patients with gynecological and soft-tissue sarcomas. Transient toxicity with myelosuppression should be accepted in order to obtain a high antitumor activity of this regimen and a potential improvement in survival.
UI - 11474287
AU - Oda Y; Miyajima K; Kawaguchi K; Tamiya S; Oshiro Y; Hachitanda Y; Oya
TI - M; Iwamoto Y; Tsuneyoshi M Pleomorphic leiomyosarcoma: clinicopathologic and immunohistochemical study with special emphasis on its distinction from ordinary leiomyosarcoma and malignant fibrous histiocytoma.
SO - Am J Surg Pathol 2001 Aug;25(8):1030-8
AD - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Pleomorphic leiomyosarcoma (PLMS) was recently described as a morphologic variant of leiomyosarcoma; however, its diagnostic criteria, as shown by morphologic features and biologic behavior, remain controversial. We describe 28 cases of pleomorphic sarcoma with pleomorphic areas in more than two thirds of the tumor and an ordinary leiomyosarcomatous fascicular area covering less than one third as PLMS. PLMS comprised 8.6% of all the leiomyosarcomas (322 cases) registered in our institute. Patients ranged in age from 31 to 89 years (average, 57.9 years). Seventeen patients (60.7%) were male and 11 were female. Tumor location was as follows: the extremities in 17 cases, the retroperitoneum or abdominal cavity in 7 cases, the chest/abdominal wall in 3 cases, and the scalp in 1 case. Histologically, all cases showed at least small foci of fascicles consisting of smooth muscle tumor cells, in addition to pleomorphic areas mimicking storiform-pleomorphic malignant fibrous histiocytoma. The border between pleomorphic and leiomyosarcomatous fascicular areas was sharp in 3 cases, gradual in 2 cases, and blending in 23 cases. Sixteen cases (57.1%) showed a typical storiform pattern, 6 cases revealed extensive stromal hyalinization, 6 cases showed a chronic inflammatory infiltrate, 2 cases had the foci of foamy xanthomatous cells, and 7 cases contained myxoid malignant fibrous histiocytoma-like areas covering less than 50% of the tumor. The tumors had a tendency to be of a morphologically higher grade (10 tumors were French Federation of Cancer Centers grade 2, 18 were grade 3). Five of 28 cases (18%) showed rhabdoid features. Immunohistochemically, all of the 28 tumors examined showed a positive reactivity for at least one smooth muscle marker (desmin, muscle-specific actin, and alpha-smooth muscle actin) in the leiomyosarcomatous fascicular areas. In the pleomorphic areas the expression of smooth muscle markers (desmin 10 of 28, muscle-specific actin 13 of 28, and alpha-smooth muscle actin 14 of 28) was significantly reduced, compared with that in leiomyosarcomatous fascicular area (desmin 18 of 28, muscle-specific actin 26 of 28, and alpha-smooth muscle actin 24 of 28). No significant difference was observed between the MIB-1 labeling index in the leiomyosarcomatous fascicular areas (26.10 on average) and that in the pleomorphic areas (26.17 on average). However, the MIB-1 labeling index in PLMS was significantly higher than that in ordinary leiomyosarcoma (n = 20, 12.86 on average) or storiform-pleomorphic malignant fibrous histiocytoma (n = 16, 16.63 on average). In 23 patients follow-up data were available with a duration of 1-239 months. Eleven patients developed metastases, and lung accounted for the most common site of metastasis (9 cases). Fifteen of 23 patients (65.2%) died of disease. Our results indicate that PLMS should be differentiated from ordinary leiomyosarcoma because of its high proliferative activities and rather aggressive biologic behavior.
UI - 11717539
AU - Watanabe K; Ogura G; Tajino T; Hoshi N; Suzuki T
TI - Myofibrosarcoma of the bone: a clinicopathologic study.
SO - Am J Surg Pathol 2001 Dec;25(12):1501-7
AD - Pathology Division, Fukushima Medical University School of Medicine Hospital, Fukishima City, Japan. firstname.lastname@example.org
Myofibroblastic tumors are fairly recently established soft tissue neoplasms. Although most of them appear to be benign, myofibrosarcoma of the soft tissue, seemingly their malignant counterpart, have been reported. We describe the clinicopathologic and radiologic features of four cases of myofibrosarcoma arising from the bone. All but one of the patients were women ranging in age from 60 to 71 years. Two tumors occurred in the metaphyses of distal femurs and the others arose in the iliac bones. On radiologic examination all tumors exhibited well-demarcated lytic destructive lesions without periosteal reaction. Two tumors were localized in the bone, whereas the other two extended into surrounding soft tissues. Histologically, all tumors were composed principally of a mixture of a cell-rich fascicular area and a hypocellular fibrous area. In the former area tumor cells had rather eosinophilic spindle-shaped wavy cytoplasm and were arranged in interlacing fascicles and small storiform patterns with variable numbers of inflammatory cells. Tumors occasionally showed prominent pleomorphism, and large cells with hyperchromatic nuclei were seen. In contrast, hypocellular areas had various features, including collagenous, hyalinous scar-like and rarely keloid-like areas. Focal coagulation necroses were present in all but one tumor. Immunohistochemically, the tumors were positive for vimentin, muscle actin (HHF35), alpha-smooth muscle actin, calponin, and desmin, whereas all of them were negative for high molecular weight caldesmon. On follow-up there was one fatal case with distant metastases, whereas the clinical courses of other cases after wide resection were excellent. Myofibrosarcoma of the bone has distinctive histopathologic features, which should be distinguished from those of other bone tumors with myoid differentiation.
UI - 11871857
AU - Brabek J; Mojzita D; Hamplova L; Folk P
TI - The regulatory region of Prague C v-Src inhibits the activity of the Schmidt-Ruppin A v-Src kinase domain.
SO - Folia Biol (Praha) 2002;48(1):28-33
AD - Department of Physiology, Charles University, Prague, Czech Republic.
Existing variants of the oncogene v-src differ in their transforming potential as well as in the range of their hosts. We compared the protein kinase activities of two Prague C v-Src variants (PRC and H19), reported to be of low oncogenic potential (Plachy et al., 1995), with the highly oncogenic Schmidt-Ruppin A v-Src (SRA). We employed in vitro kinase assays of affinity-purified proteins expressed in rabbit reticulocyte lysate and in S. cerevisiae. In both systems used, the specific kinase activity of the Prague C v-Src kinases amounted to only ca 20% of the activity of SRA. This positions the PRC Src close to activated c-Src, despite the lack of the regulatory C-terminal tail in PRC. We constructed chimeras between PRC and SRA v-Src and tested them for specific kinase activity in S. cerevisiae. Remarkably, the regulatory N-terminal part of PRC, when fused to the SRA-derived kinase domain, lowered the chimeras' PK activity to ca 20%, suggesting that it is the regulatory part of PRC that is responsible for its low phosphotransferase activity.
UI - 11876388
AU - Szabo I; Szantho A; Csabay L; Csapo Z; Szirmai K; Papp Z
TI - Color Doppler ultrasonography in the differentiation of uterine sarcomas from uterine leiomyomas.
SO - Eur J Gynaecol Oncol 2002;23(1):29-34
AD - Department of Obstetrics and Gynaecology, Semmelweis University Medical School, Budapest, Hungary.
OBJECTIVE: The aim of this study was to investigate uterine vascularity in cases of uterine leiomyomas and uterine sarcomas, as well as to determine the efficiency of uterine blood flow analysis in differentiating between them. MATERIALS AND METHODS: Transvaginal color and pulsed Doppler findings obtained from 117 patients with histologically proven uterine leiomyoma and 12 with uterine sarcoma were retrospectively assessed. RESULTS: The mean intratumoral resistance index (RI) and pulsatility index (PI) were significantly lower and the intratumoral peak systolic velocity (PSV) was significantly higher in patients with sarcomas than in patients with uterine leiomyomas. Marked reduction of RI and PI and increased PSV could be found in 14 of the leiomyoma cases which showed large size and/or necrotic, degenerative and inflammatory changes. When a cut-off value of 0.5 for the RI was considered, the detection rate for uterine sarcoma was 67% and the false-positive rate was 11.8%. CONCLUSION: These results suggest that the intratumoral RI detected by color and pulsed Doppler ultrasonography in themselves could be poor for the preoperative differential diagnosis of uterine sarcoma.
UI - 12082855
AU - Nielsen OS; Keller JO; Dombernowsky P
TI - [Sarcomas]
SO - Ugeskr Laeger 2002 Jun 3;164(23):3036-9
AD - Arhus Universitetshospital, Arhus Kommunehospital, onkologisk afdeling, ortopaedkirurgisk afdeling.
UI - 12088451
AU - Boyle JL; Haupt HM; Stern JB; Multhaupt HA
TI - Tyrosinase expression in malignant melanoma, desmoplastic melanoma, and peripheral nerve tumors.
SO - Arch Pathol Lab Med 2002 Jul;126(7):816-22
AD - Department of Pathology, Pennsylvania Hospital, Philadelphia, PA 19107, USA.
CONTEXT: Pathologists may encounter problems in the differential diagnosis of malignant melanoma, spindle and epithelioid neoplasms of peripheral nerves, and fibrohistiocytic tumors. Tyrosinase has been demonstrated to be a sensitive marker for melanoma. OBJECTIVE: To determine the specificity of tyrosinase expression in the differential diagnosis of melanoma, desmoplastic melanoma, and peripheral nerve sheath tumors. DESIGN: Immunoreactivity for tyrosinase, HMB-45 (anti-gp100 protein), S100 protein, CD34, and vimentin was studied in 70 tumors, including 15 melanomas (5 desmoplastic, 4 amelanotic, 6 melanotic), 13 malignant peripheral nerve sheath tumors; 10 schwannomas (1 pigmented), 12 neurofibromas (4 pigmented), and 20 fibrohistiocytic tumors (10 dermatofibrosarcoma protuberans and 10 dermatofibromas). Microwave-based antigen retrieval was performed in 10mM citrate buffer, pH 6.0, for 20 minutes at 121 degrees C. RESULTS: All melanomas demonstrated positive immunostaining for tyrosinase, HMB-45, and S100 protein. Immunoreactivity for HMB-45 was generally stronger than that for tyrosinase in amelanotic lesions and significantly stronger in 1 of the desmoplastic lesions. The 4 pigmented neurofibromas were focally positive for tyrosinase, but did not stain for HMB-45. The pigmented schwannoma was focally positive for both tyrosinase and HMB-45. The malignant peripheral nerve sheath tumors, dermatofibrosarcoma protuberans, and dermatofibromas were nonreactive for tyrosinase and HMB-45. CONCLUSIONS: Our results support the sensitivity of tyrosinase expression and demonstrate the relative specificity of tyrosinase as a marker for melanocytic lesions, including desmoplastic melanoma, although pigmented peripheral nerve tumors may demonstrate focal positive staining. Immunoreactivity for tyrosinase and HMB-45 may have been enhanced by the microwave-based antigen-retrieval technique used in this study.
UI - 12091061
AU - van Ruth S; van Coevorden F; Peterse JL; Kroon BB
TI - Alveolar soft part sarcoma. a report of 15 cases.
SO - Eur J Cancer 2002 Jul;38(10):1324-8
AD - Department of Surgery, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 120, 1066 CX Amsterdam, The Netherlands.
The aim of this study was to evaluate the presentation, course and treatment outcome of 15 patients with this rare type of sarcoma. The files of the patients were retrospectively analysed. Overall survival was calculated according to the Kaplan-Meier method. There were 15 patients, 8 male and 7 female. The mean age at diagnosis was 29 years for men and 24 years for women. The median survival was 48 months with an overall 5-year survival of 38%. 5 patients had haematogenic metastases at the time of diagnosis. For the remaining 10 patients with localised disease, the median survival was 48 months and the 5-year survival 48%. The median disease-free survival for these patients was 12 months with a 5-year disease free survival of 40%. After the occurrence of haematogenic metastases, patients survived a median period of 8 months (range 0-45 months). 5 patients are still free of disease after a median period of 234 months (12-295 months). Alveolar soft part sarcoma is found especially in young adults. When diagnosed, it is often metastasised with a poor prognosis. However, when radically resected, long-term survival is possible.
UI - 12091063
AU - Merimsky O; Issakov J; Bickels J; Kollender Y; Flusser G; Soyfer V;
TI - Schwartz I; Inbar M; Meller I ErbB-4 expression in limb soft-tissue sarcoma: correlation with the results of neoadjuvant chemotherapy.
SO - Eur J Cancer 2002 Jul;38(10):1335-42
AD - Department of Oncology, The Tel-Aviv Sourasky Medical Center, 6 Weizman Street, Israel. email@example.com
ErbB-4 is a recently described growth factor receptor. Relatively little is known about its expression in human tumours. In this study, we assessed the possible role of erbB-4 as a tissue marker for soft-tissue sarcomas (STS) and its correlation with the response to chemotherapy. The histological specimen of 29 patients with STS of a limb who had received preoperative doxorubicin (ADR)-based chemotherapy were studied for the degree of necrosis and the expression of erbB-4 (by an avidin-biotin-peroxidase technique). ErbB-4 expression in the preoperative tissue samples was compared with the expression in the postchemotherapy resected tumour. The true objective response rate to preoperative chemotherapy was 34%. Wide resection of the tumour was done in 12 patients, marginal in 14, amputation in 2 and no surgery in 1. The tumour necrosis was above 90% in 9 patients, 60-90% in 12, and less than 60% in 7 patients. An increase in erbB-4 expression was more common in cases with no response to chemotherapy, while no change or a decrease in erbB-4 was more common in responsive tumours (P=0.004). No correlation could be found between the degree of necrosis or the chemotherapeutic regimen and the change in expression of erbB-4. The median disease-free survival (DFS) was longer for patients with a decrease or no change in expression of erbB-4 than for patients with increased expression. It is believed that postchemotherapy new expression or no downregulation of the erbB-4 molecule represents tumour aggressiveness and increased capability of growth and spread.
UI - 12150740
AU - Wei Y; Wang J; Zhu X; Shi D; Hisaoka M; Hashimoto H
TI - Detection of SYT-SSX fusion transcripts in paraffin-embedded tissues of synovial sarcoma by reverse transcription-polymerase chain reaction.
SO - Chin Med J (Engl) 2002 Jul;115(7):1043-7
AD - Department of Pathology, Cancer Hospital, Fudan University, Shanghai 200032, China.
OBJECTIVE: To assess the feasibility of detecting SYT-SSX fusion transcripts in paraffin-embedded tissues of synovial sarcoma by reverse transcription-polymerase chain reaction (RT-PCR). METHODS: RT-PCR was used to amplify the SYT-SSX fusion transcripts using archival formalin-fixed paraffin-embedded tumor specimens from a series of 37 synovial sarcoma cases. To investigate the specificity of the SYT-SSX fusion transcripts, a variety of non-synovial sarcoma tumors were included in the study as negative controls. The detected messages derived from fusion genes were confirmed by subsequent sequence analysis. RESULTS: SYT-SSX fusion transcripts were detected in 33 of 37 (89.2%) synovial sarcomas. None of the 34 cases of non-synovial sarcoma tumors showed amplified products of SYT-SSX fusion transcripts, although PBGD mRNA was detected in all specimens. Among 33 SYT-SSX-positive synovial sarcomas, 22 tumors had an SYT-SSX 1 fusion transcript, whereas 6 tumors had an SYT-SSX2 fusion transcript. Fusion types can not be distinguished in the remaining 5 cases. There was a significant relationship between SYT-SSX fusion type and histologic subtype. All 10 biphasic synovial sarcomas had the SYT-SSX1 fusion, whereas all tumors with SYT-SSX2 were of monophasic morphology (P < 0.05). CONCLUSIONS: RT-PCR can be applied to archival formalin-fixed paraffin-embedded tumor tissues as a sensitive and reliable technique for the diagnosis and differential diagnosis of synovial sarcoma. There is an association between SYT-SSX fusion type and histological subtype. SYT-SSX2 fusion transcripts can only be found in monophasic synovial sarcoma.
UI - 12171492
AU - Lu C; Gordon GM; Chandran B; Nickoloff BJ; Foreman KE
TI - Human herpesvirus 8 reactivation and human immunodeficiency virus type 1 gp120.
SO - Arch Pathol Lab Med 2002 Aug;126(8):941-6
AD - Department of Pathology and Skin Cancer Research Laboratories, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, Ill 606153, USA.
CONTEXT: Human herpesvirus 8 (HHV-8) is the presumed etiologic agent of Kaposi sarcoma (KS), the most common neoplasm in patients with acquired immunodeficiency syndrome. Current evidence indicates HHV-8 is necessary, but not sufficient, for KS development without the involvement of other cofactors. One potentially important cofactor is human immunodeficiency virus type 1 (HIV-1). Although HIV-1 is not essential for development of KS, studies have shown factors released from HIV-1-infected cells, including HIV-1 proteins and cytokines, promote the growth of KS cells in vitro. Recently, studies have shown that coculture of HIV-1-infected T cells with HHV-8-infected primary effusion lymphoma cell lines results in HHV-8 reactivation. This response was due, in part, to cytokines. However, only a portion of induced HHV-8 replication could be accounted for by cytokine stimulation, indicating that other factors, including HIV-1-associated proteins, may also be involved. OBJECTIVE: To investigate a possible role for HIV-1 gp120 in HHV-8 reactivation. DESIGN: Using an in vitro model system, we examined the effect of recombinant HIV-1 gp120 protein on HHV-8 replication in latently infected primary effusion lymphoma cell lines. MAIN OUTCOME MEASURES: Reactivation of HHV-8 was analyzed using Northern blot analysis and quantitative polymerase chain reaction for ORF26 messenger RNA expression, a gene encoding for the HHV-8 minor capsid protein produced only during reactivation. The results were extended and confirmed using a luciferase reporter construct driven by the HHV-8 ORF50 promoter, the first promoter activated during HHV-8 replication. RESULTS: No evidence of enhanced HHV-8 replication was found following treatment with HIV-1 gp120. In addition, HIV-1 gp120 was unable to act synergistically with interferon-gamma or hepatocyte growth factor/scatter factor to enhance reactivation of the virus in infected primary effusion lymphoma cell lines. CONCLUSIONS: HIV-1 gp120 does not appear to be responsible for the reactivation of HHV-8 demonstrated in our previous studies. Further studies are necessary to determine if other HIV-associated proteins, particularly Tat, gp160, and/or gp41, which are also released from infected cells, may be important in inducing HHV-8 reactivation.
UI - 12173050
AU - Xie Y; Skytting B; Nilsson G; Grimer RJ; Mangham CD; Fisher C; Shipley
TI - J; Bjerkehagen B; Myklebost O; Larsson O The SYT-SSX1 fusion type of synovial sarcoma is associated with increased expression of cyclin A and D1. A link between t(X;18)(p11.2; q11.2) and the cell cycle machinery.
SO - Oncogene 2002 Aug 22;21(37):5791-6
AD - Department of Oncology and Pathology, CCK R8: 04, Karolinska Hospital, Stockholm, Sweden.
A recent large multi-centre study convincingly confirmed previous observations that the SYT-SSX1 fusion type, compared to SYT-SSX2, of synovial sarcoma is associated with a worse clinical outcome. Apart from the clinical impact, this fact also suggests (1) that the SYT-SSX fusion gene may influence molecular mechanisms involved in tumour growth and progression; and (2) that the SYT-SSX1 fusion type has a stronger influence on these mechanisms than SYT-SSX2. The nature of the underlying mechanisms is, however, still unknown. In this study we made use of the SYT-SSX1 vs SYT-SSX2 concept to investigate whether major, tumour relevant, and growth regulatory proteins (e.g. cyclins and cyclin-dependent kinases) may be involved. Using Western blotting analysis on 74 fresh, fusion variant-typed, tumour samples from localized synovial sarcoma, we found a significant correlation between SYT-SSX1 and high expression of cyclin A (P=0.003) and D1 (P=0.025). Our data suggest that SYT-SSX may influence the cell cycle machinery, and that the more aggressive phenotype of the SYT-SSX1 variant is due to an accelerated tumour cell proliferation.
UI - 12185060
AU - Israel GM; Bosniak MA; Slywotzky CM; Rosen RJ
TI - CT differentiation of large exophytic renal angiomyolipomas and perirenal liposarcomas.
SO - AJR Am J Roentgenol 2002 Sep;179(3):769-73
AD - Department of Radiology, Division of Abdominal Imaging, HW 202, New York University Medical Center, 560 First Ave., New York, NY 10016, USA.
OBJECTIVE: The purpose of our study was to describe the imaging findings and CT characteristics that lead to accurate distinction of large exophytic renal angiomyolipomas from retroperitoneal perirenal liposarcomas, which at times can be confused on imaging studies and even at pathologic examination. MATERIALS AND METHODS: We retrospectively analyzed CT images of 15 large exophytic renal angiomyolipomas and 12 well-differentiated perirenal liposarcomas. Pathologic correlation was available for six of 15 angiomyolipomas and all of the liposarcomas. All examinations were evaluated for lesion size, renal parenchymal defect, enlarged vessels, kidney displacement, lesion encapsulation or margination, associated hemorrhage, and additional angiomyolipomas. The records of patients with tuberous sclerosis or the forme fruste of that condition were excluded from the study. RESULTS: The average size of the angiomyolipomas was 14 x 10 cm. They showed a renal parenchymal defect (n = 15), enlarged vessels (n = 12), renal displacement (n = 14), good margination without a distinct capsule (n = 14), hemorrhage (n = 1), and additional (one or two) angiomyolipomas (n = 4). The average size of the liposarcomas was 18 x 11.6 cm. They showed enlarged vessels (n = 3), renal displacement (n = 11), and encapsulation (n = 4); none showed a renal parenchymal defect, hemorrhage, or associated angiomyolipomas. CONCLUSION: Although large exophytic angiomyolipomas and well-differentiated retroperitoneal liposarcomas may have similar appearances on imaging, careful evaluation for a defect in the renal parenchyma combined with the presence of enlarged vessels in angiomyolipomas should enable accurate differentiation in almost all cases. Achieving an accurate diagnosis can have a significant impact on patient treatment.
UI - 12185067
AU - McCarville MB; Spunt SL; Skapek SX; Pappo AS
TI - Synovial sarcoma in pediatric patients.
SO - AJR Am J Roentgenol 2002 Sep;179(3):797-801
AD - Department of Diagnostic Imaging, Mail Stop 210, St. Jude Children's Research Hospital, 332 N. Lauderdale St., Memphis, TN 38105-2794, USA.
UI - 12177782
AU - Barker KT; Bevan S; Wang R; Lu YJ; Flanagan AM; Bridge JA; Fisher C;
TI - Finlayson CJ; Shipley J; Houlston RS Low frequency of somatic mutations in the FH/multiple cutaneous leiomyomatosis gene in sporadic leiomyosarcomas and uterine leiomyomas.
SO - Br J Cancer 2002 Aug 12;87(4):446-8
AD - Section of Cancer Genetics, Haddow Laboratories, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
Germline mutations in the fumarate hydratase gene at 1q43 predispose to dominantly inherited skin and uterine leiomyomata and leiomyosarcomas. The enzyme, which is a component of the tricarboxylic acid cycle, acts as a tumour suppressor. To evaluate fumarate hydratase in respective sporadic tumours, we analysed a series of 26 leiomyosarcomas and 129 uterine leiomyomas (from 21 patients) for somatic mutations in fumarate hydratase and allelic imbalance around 1q43. None of the 26 leiomyosarcomas harboured somatic mutations in fumarate hydratase. Fifty per cent of leiomysarcomas tested showed evidence of allelic imbalance at 1q, but this was not con