[Value of aortography in the diagnosis of non-organic retroperitoneal tumors].
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During the past two decades we have witnessed the identification of an expanding list of immunohistochemical and molecular markers linked to histopathologically defined subtypes of tumors. These markers offer new insights and approaches to the classification of tumors with important prognostic and/or therapeutic implications. We review the potentially diagnostic immunohistochemical and molecular markers of soft tissue tumors (STTs). The immunohistochemical markers reviewed include vimentin, cytokeratin, desmin, HHF35, S100, myoD1, alpha1-antitrypsin, vascular markers (factor VIII, CD31, CD34), MIC2, and others. The potentially diagnostic chromosomal translocations and associated genes identified in STT include Ewing's/PNET t(11;22)(q24;q12)(FLI1;EWS), t(21;22)(q22;q12)(ERG; EWS); t(7;22)(p22;q12)(ETV1;EWS); desmoplastic small round cell tumor t(11;22)(p13;q12)(WT1;EWS); extraskeletal myxoid chondrosarcoma t(9;22)(q22;q12) (TEC(CHN);EWS); malignant ectomesenchymoma t(11;22)(q24;q12)(FLI1;EWS); alveolar rhabdomyosarcoma t(2;13)(q35;q14)(PAX-3;FKHR); t(1;13) (p36;q14)(PAX-7;FKHR); myxoid and round cell liposarcoma t(12;16)(q13;p11)(CHOP;TLS(FUS)); synovial sarcoma t(X;18)(p11;q11)(SSX1&2;SYT), and others. The nature, utility, and limitations of these markers in diagnostic settings are explored.
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To determine whether serum beta 2-microglobulin values could be useful as a tumor marker in patients with soft tissue sarcomas, 31 preoperative sera stored in our serum bank were assayed by radioimmunoassay for beta 2-microglobulin levels. Sera were selected from patients known to have large bulky tumors, but no evidence of other major systemic disorders. Thirty-one sera of sex and age matched controls were assayed for comparison. The laboratory range for normal serum beta 2-microglobulin values was 1.1-2.4 mg/l. Our control patients had values ranging from 0.7-1.7 mg/l. Values in tumor patients ranged from 0.7-2.5 mg/l. No markedly elevated values were observed in any single patient. Four age groups, 20-29, 30-39, 40-49, and 50-59 years, revealed no significant differences. This observation differs from previously reported data. Serum beta 2-microglobulin appears to have no value as a tumor marker in patients with soft tissue sarcomas. We were unable to substantiate findings by others that there is a significant increase in values of normal subjects corresponding to advancing age.
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FUS (TLS) was first identified as the 5'-part of a fusion gene with CHOP (GADD153, DDIT3) in myxoid liposarcomas with t(12; 16)(q13; p11). Homologies were found with the EWS oncogene, which is rearranged in Ewing sarcomas and other neoplasias. The genomic structure of FUS shows extensive similarities with that of EWS, but the exon/intron structures differ in the 5' parts, and overall FUS is smaller than EWS. Exon 3 of FUS corresponds to exons 3 and 4 in EWS. FUS exons 4-6 correspond to EWS exons 5-8. Exons 7 to 15 of FUS are very similar to those in EWS, although the EWS exons are larger than the corresponding FUS exons. FUS and EWS were expressed in all tissues investigated. The transcripts were stable within the 160-min half-life experiments. No or little variation in FUS or EWS expression was seen when resting lymphocytes were activated. These observations indicate that FUS and EWS belong to the housekeeping type of genes. This view is supported by the presence of the housekeeping gene type of promoter region in both genes.
BACKGROUND: The expression of the human Eag1 potassium channel (Kv10.1) is normally restricted to the adult brain, but it has been detected in both tumour cell lines and primary tumours. Our purpose was to determine the frequency of expression of Eag1 in soft tissue sarcoma and its potential clinical implications. RESULTS: We used specific monoclonal antibodies to determine the expression levels of Eag1 in soft tissue sarcomas from 210 patients by immunohistochemistry. Eag1 was expressed in 71% of all tumours, with frequencies ranging from 56% (liposarcoma) to 82% (rhabdomyosarcoma). We detected differences in expression levels depending on the histological type, but no association was seen between expression of this protein and sex, age, grade or tumour size. Four cell lines derived from relevant sarcoma histological types (fibrosarcoma and rhabdomyosarcoma) were tested for Eag1 expression by real-time RT-PCR. We found all four lines to be positive for Eag1. In these cell lines, blockage of Eag1 by RNA interference led to a decrease in proliferation. CONCLUSION: Eag1 is aberrantly expressed in over 70% sarcomas. In sarcoma cell lines, inhibition of Eag1 expression and/or function leads to reduced proliferation. The high frequency of expression of Eag1 in primary tumours and the restriction of normal expression of the channel to the brain, suggests the application of this protein for diagnostic or therapeutic purposes.
Fifteen patients with large (average, 15-cm), high-grade soft-tissue sarcomas of the extremities received prolonged selective intraarterial infusions of chemotherapeutic agents in an attempt to permit limb-sparing resection of these tumors, which would otherwise have required amputation. There were seven malignant fibrous histiocytomas, four liposarcomas, two fibrosarcomas, one leiomyosarcoma, and one rhabdomyosarcoma; 73% were grade III. Seven patients underwent two catheterizations, for a total of 22 infusions, which averaged 11.3 days each. There were four catheterization-related complications, including catheter occlusion or dislodgement in one patient each and two cases of arterial thromboembolism in patients in whom anticoagulant dose was not adequate. Both of the latter patients required thrombectomy; one developed gangrene, which precluded limb-sparing surgery. Thirteen of the 15 patients underwent limb-sparing resections, and two underwent amputations. No wound complications occurred. With a median follow-up of 36 months (mean, 34 months), life-table analysis indicates overall and disease-free survivals of 72% and 59%, respectively, at 2 years and 64% and 59% at 3 years. In comparison to other reported therapies, this technique permits limb salvage in most patients without the high wound complication rate associated with preoperative radiation therapy, with equivalent local disease control and survival.
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Cutaneous sarcomas are uncommon tumors presenting many histological types. The diagnosis is based on pathological, immunohistochemical and sometimes ultrastructural studies. The development of cytogenetic and molecular analysis may constitute an additional aid to the diagnosis and classification. Prognosis and therapeutic strategies are established on the basis of various criteria using different types of staging and grading, but these classifications have not yet been standardized. The rarity of cutaneous sarcoma, and the diversity of clinical presentations account for the difficulties of management, which requires a multidisciplinary approach.
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PURPOSE: We evaluate the outcome, clarify the patterns of failure and suggest treatment strategies for sarcoma in the spermatic cord. MATERIALS AND METHODS: Between 1956 and 1998, 32 patients with spermatic cord sarcoma were treated at M. D. Anderson Cancer Center. A retrospective review of disease outcome, patterns of relapse and patient survival was performed. RESULTS: Histological subtypes of sarcoma were malignant fibrous histiocytoma in 12 patients, leiomyosarcoma in 6, liposarcoma in 8 and other subtypes in 6. All except 2 patients underwent radical orchiectomy with or without additional resection to achieve negative margins. Margins were microscopically negative in 29 cases and positive in 3. There were 3 patients who received adjuvant radiation to the surgical site. With a median followup of 9 years the 10 and 15-year actuarial local control, distant metastasis-free and overall survival rates were 72% and 61%, 85% and 85%, and 63% and 52%, respectively. The major pattern of failure was local recurrence that occurred in 8 of the 12 patients in whom disease relapsed and was the sole site of relapse in 7. Pelvic nodes had relapsed in 2 patients and para-aortic nodes in 1. Hematogenous metastases had developed in 4 patients. Of the 7 cases of disease that recurred locally only 3 were salvaged. No relapse occurred in the 3 patients treated with combined surgery and radiation. CONCLUSIONS: Spermatic cord sarcoma has a high propensity for local recurrence after surgery. Nodal relapse is less frequent than commonly believed. Because of the relatively high local failure rate seen in surgery alone and durable local control noted in 3 patients treated with surgery plus radiotherapy, combined modality treatment should be considered in those with spermatic cord sarcoma who are believed to be at high risk for local failure.
The cadherin-mediated cell-cell adhesion system is now known to play a critical role in both the morphogenesis of cancer cells and suppression of their invasion. However, the pattern of expression of E-cadherin, the major cadherin of epithelial cells in bone and soft tissue sarcomas, remains unclear. This prompted us to study E-cadherin expression in a variety of bone and soft tissue sarcomas. Using the monoclonal antibody HECD-1, raised against the extracellular domain of E-cadherin, we observed immunoreactivity in 1 pleomorphic rhabdomyosarcoma, 2 of 5 diffuse mesotheliomas, 4 of 5 clear cell sarcomas, 1 of 5 epithelioid sarcomas, and 10 synovial sarcomas. Other types of bone and soft tissue sarcoma (4 osteosarcomas, 4 chondrosarcomas, 3 primitive neuroectodermal tumors, 1 fibrosarcoma, 4 malignant fibrous histiocytomas, 5 liposarcomas, 4 leiomyosarcomas, 6 alveolar and 5 embryonal rhabdomyosarcomas, 4 angiosarcomas, 4 malignant peripheral nerve sheath tumors, 2 extraskeletal myxoid chondrosarcomas, 2 extraskeletal osteosarcomas, and 3 alveolar soft part sarcomas) were completely negative for E-cadherin. Our findings indicate that E-cadherin is expressed in certain kinds of soft tissue sarcomas, especially those with epithelioid features, suggesting that E-cadherin plays a role in the constitution of their architecture.