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PubMed2006

Diagnosis of clear cell sarcoma by real-time reverse transcriptase-polymerase chain reaction analysis of paraffin embedded tissues: clinicopathologic and molecular analysis of 44 patients from the French sarcoma group.

BACKGROUND: Clear cell sarcoma (CCS) is a rare tumor with a very poor prognosis that occurs predominantly in the distal extremities of young adults. Most patients bear the t(12;22) reciprocal translocation, which involves the EWS and ATF1 genes. The diagnosis of CCS usually is easy but may be challenging in unusual sites, and the detection of EWS-ATF1 fusion transcripts is helpful to rule out a metastatic melanoma. METHODS: Forty-four patients with CCS and 14 conventional melanomas were examined for the presence of EWS-ATF1 transcripts by using real-time polymerase chain reaction (PCR) analysis on paraffin embedded tissues, including frozen samples for 9 CCS samples and 9 melanoma samples. Prior to molecular analysis, the diagnosis of CCS was considered certain in 35 patients and as probable in 9 patients on the basis of location, histologic features, and immunohistochemical profile. Treatment modalities and follow-up were available for 41 patients with CCS. RESULTS: EWS-ATF1 fusion transcripts were detected in 38 paraffin embedded CCS tissues (86% of all samples; 93% of interpretable samples), 3 samples (7%) were negative, and 3 samples (7%) were considered uninterpretable. Fusion transcripts were detected in 7 of 9 samples for which the diagnosis of CCS was considered probable. EWS-ATF1 transcripts were not detected in the 14 samples of melanoma. Results from frozen tissues were concordant with those from all corresponding paraffin embedded samples. Twenty-eight of 41 patients (68%) experienced lymph node and/or distant metastasis, and the 5 year-survival rate was 44%. Mitotic index and histologic grade were predictive of survival and distant metastasis. CONCLUSIONS: The results of this study showed that the molecular detection of EWS-ATF1 fusion transcript by real-time PCR on paraffin embedded tissues is a sensitive and specific method for the diagnosis of CCS. It is an efficient tool for the diagnosis of unusual tumors, especially with regard to its distinction from melanoma. The current results also confirmed the poor prognosis for patients with this tumor type. Mitotic index and grade were predictive factors for survival and distant metastasis.

Adolescent↗

PubMed1975

Cell-mediated immunity to Moloney sarcoma virus in mice. II. Analysis of antigenic specificities involved in T lymphocyte-mediated in vivo rejection of murine sarcoma virus-induced tumors.

Sublethally irradiated BALB/c mice innoculated with Moloney sarcoma virus (MSVm) develop progressively growing tumors and die within 30 days of virus innoculation. These animals can be protected from tumor progression (and death) by innoculation of small numbers of MSV-immune T lymphocytes from MSV-M innoculated (but unirradiated) animals. T lymphocytes in these donor animals have been shown to express immunity to a variety of viral and virally-induced antigens. We have investigated whether immunity to any one of these antigens was critically important in leading to protection of the irradiated animals by sensitizing normal T lymphocytes in vitro to different viral antigens and examining the ability of these sensitized cells to protect the irradiated recipients. Data is presented to show that cells sensitized in vitro to MSV-transformed fibroblasts, and to purified antigens with group specificity, but not to viral envelope antigens, or whole virus, are capable of protecting the irradiated MS innoculated animals.

Animals↗

PubMedDate not supplied

Head and neck sarcoma: report of the Head and Neck Sarcoma Registry. Society of Head and Neck Surgeons Committee on Research.

A Head and Neck Sarcoma Registry was established by the Society of Head and Neck Surgeons to review treatment results of a rare tumor by surgeons with special interest in this anatomic site. Two hundred fourteen patients were analyzed. There were 194 adult tumors and 20 pediatric tumors. The major sites included parotid and neck, 20%; face and forehead, 18%; maxilla and palate, 13%; scalp, 12%; mandible, 11%; paranasal sinuses, 7%; larynx, 2%; and oral cavity, 5%. Eighty-four percent were resectable. The disease-free survival was 56%; overall survival was 70% at 5 years. Major determinants of survival were adequacy of resection (margins free of tumor) and tumor type. Survival differed according to tumor cell type (tumor grade was not available). Patients with chondrosarcoma and dermatofibrosarcoma had survival approaching 100%. Patients with malignant fibrous histiocytoma (MFH) and fibrosarcoma (FSA) had intermediate survival of 60% to 70%. The worst survival, less than 50% at 5 years, occurred in patients with osteosarcoma, angiosarcoma, and rhabdomyosarcoma in decreasing order. This suggests a rationale for identifying high-risk patients for prospective adjuvant protocols. This study emphasizes the value of recording uncommon tumors to provide relevant information for future study and possibly therapy.

Adolescent↗

PubMed1975

Antibody patterns to herpesviruses in kaposi's sarcoma: serological association of european kaposi's sarcoma with cytomegalovirus.

Sera from patients with Kaposi's sarcoma (KS) were examined for antibody titres to cytomegalovirus (CMV), Epstein-Barr virus (EBV) and herpes simplex virus (HSV) types 1 and 2 by four techniques: indirect haemagglutination (IHA), complement fixation (CF), virus neutralization (NT) and indirect immunofluorescence (IF). The patients were classified, according to the stage of disease, as progressive and regressive. Control sera were obtained from healthy adults, matched for age, sex, race, socioeconomic status and geographic location, as well as from patients with melanoma, some of whom were receiving chemotherapy similar to that given to the KS patients. All KS sera contained CMV-neutralizing antibodies. Seventy-five percent of the European KS patients, mainly regressors, showed elevated anti-CMV titres by IHA with a significant increase in the geometric mean over the corresponding healthy adult group and the melanoma group. An overrepresentation of high anti-CMV titres, although less marked, was found by CF. There was no significant association with antibodies to EBV, HSV-1 and HSV-2 related antigens. By contrast, the African KS patients, mainly progressors, did not show a serologic association with CMV or with EBV and HSV-1 and 2. The implication of these results is discussed.

Adult↗

PubMed1978

Antibody patterns to herpesviruses in Kaposi's sarcoma. II. Serological association of American Kaposi's sarcoma with cytomegalovirus.

The prominent finding of this extended serologic analysis on American and African Kaposi's sarcoma (KS) patients and appropriately matched control groups is the detection of a specific serologic association of cytomegalovirus (CMV) with American KS patients. All American KS sera contained CMV antibodies and their geometric mean titers (GMT) were significantly higher than those in sera of melanoma patients (GMT ratio k = 5.3 to 7.7 by complement fixation [CF], k = 8.9 by indirect hemagglutination [IHA]) or in sera of age- and sex-matched healthy controls (k = 12.6 to 16.0 by CF, k = 12.6 by IHA). The result is strongly reminiscent of the data obtained previously for European KS. Although the GMT to CMV of African KS patients were similar to the GMT of the American KS groups, their significance cannot be demonstrated due to the high background of CMV infections in the control groups. Complex mechanisms are hypothesized, by analogy with the Epstein-Barr virus (EBV) involvement in Burkitt's lymphoma (BL), for a CMV involvement in the development of KS.

Aged↗

PubMed2004

Salvage surgical resection after high-dose ifosfamide (HDIF) based regimens in advanced soft tissue sarcoma (ASTS): a potential positive selection bias--a study of the Spanish group for research on sarcomas (GEIS).

PURPOSE: To assess the impact of different factors on response rate (RR), time to tumor progression (TTP), and overall survival time (OS) in patients with locally advanced or metastatic soft tissue sarcoma (ASTS), included in three protocols with high-dose ifosfamide (HDIF). PATIENTS AND METHODS: One hundred fifty six ASTS patients included in three consecutive phase II trials with HDIF (>10 g/m(2)), alone or in combination with doxorubicin (DX), were analyzed. Cofactors were institution, trial, gender, age, performance status, histologic type, grade of malignancy, prior radiotherapy, presence of locoregional disease, metastatic site, salvage surgery, number of organs involved, and disease-free interval. RESULTS: By multivariate analysis performance status >0 and lack of salvage surgery correlated with a poorer survival. A good-risk and a poor-risk group were identified, with median survival time (OS) of 29, 5, and 10 months, respectively (P = 0.00001). The 1-, 2-, and 3-year OS for 83 good-risk patients (either with PS = 0 or receiving salvage surgery) was 83, 44, and 29%, respectively, those figures being 37, 7, and 3% for 73 poor-risk patients. CONCLUSION: The design of randomized trials in ASTS including HDIF should consider those prognostic factors as stratification variables.

Adult↗

PubMed1989

Extremity soft tissue sarcomas: analysis of prognostic variables in 300 cases and evaluation of tumor necrosis as a factor in stratifying higher-grade sarcomas.

From July 1975 to February 1985, 300 patients with extremity soft tissue sarcomas (STS) were entered into treatment protocols at the National Cancer Institute. Using the Cox proportional hazards model, the STS were analyzed for independent prognostic variables that had significant association with disease-free and overall survival. The effects of adjuvant treatment were also included in the analysis. Percent tumor necrosis was the basis for separating intermediate and high-grade STS (less than 15% necrosis = grade 2; greater than 15% necrosis = grade 3). The most important prognostic variable was histologic grade, which was highly associated with relative risk of metastasis and fatal outcome (P less than .0001). Histologic type of STS was not a significant prognostic variable in predicting metastases. Patients with tumors located on the proximal or middle part of the extremity had a fivefold increased risk of death (P = .02) compared with patients who had STS located more distally. Mitotic activity (P = .0005) and vascular invasion (P = .0034) were also associated with malignant behavior, but histologic grade was the most significant predictor of outcome. Histologic grade of malignancy was based upon a combination of tumor typing and visual estimation of extent of tumor necrosis; using these two features, one can reliably separate low-grade (i.e., grade 1) from high-grade STS and also stratify the more aggressive (i.e., grade 2 and 3) tumors. Over the 9.5-year period of study, the tumor-related mortality was as follows: grade 1 (1/38), 3%; grade 2 (19/142), 13%; and grade 3 (45/120), 38%.

Adult↗

PubMed1989

Soft tissue sarcomas in infants younger than 1 year of age: a report of the German Soft Tissue Sarcoma Study Group (CWS-81).

Of 357 patients with soft tissue sarcomas (STSs) who were registered between 1981 and 1986 in the CWS-81 study, 21 (5.8%) were younger than 1 year of age. Six cases were probably of congenital origin since they were diagnosed in the 1st month of life. There was no difference in clinical grouping (staging and primary site) between infants and older patients. The major histological subsets comprised 12 patients with embryonal rhabdomyosarcoma (57% vs. 44% in older patients) and five patients with fibrosarcoma (23% vs. 2% in older patients). Of 21 patients, 17 received chemotherapy. The response rate (tumor reduction more than 1/3) to exclusive cytostatics therapy within 7-9 weeks, of ten evaluable patients, was 100% (vs. 86% in older patients). Eight of the responders achieved complete remission after 16 weeks of therapy and are in continuous complete remission (CCR). Most patients received 20-50% of the recommended chemotherapy dose for older children, which was calculated using body surface area. No fatal or life-threatening complications were observed. The event-free survival rate for children younger than 1 year of age with rhabdomyosarcoma was 70% vs. 47% in older children (no significant difference). Now, 2-5 years after therapy all five fibrosarcoma patients are alive and free of disease. Our data indicate that children under 1 year of age with rhabdomyosarcoma have a slightly better prognosis than older children, when therapy modalities are adapted to age.

Age Factors↗

PubMed2006

Grossly-resected synovial sarcoma treated by the German and Italian Pediatric Soft Tissue Sarcoma Cooperative Groups: discussion on the role of adjuvant therapies.

Differently from adult oncologists that considered synovial sarcoma (SS) a tumor with uncertain chemosensitiveness, since two decades pediatric oncologists in Europe assumed that chemotherapy played an important role in SS treatment, so most pediatric patients were included in rhabdomyosarcoma protocols, receiving adjuvant chemotherapy regardless of risk factors. The German and Italian groups reviewed the data of grossly resected SS patients in order to define a risk-adapted treatment program for the next European protocol. A total of 150 patients < 21 years with localized SS who underwent initial gross resection between 1975 and 2002 were the object of this study. All but four cases received adjuvant chemotherapy. Post-operative radiotherapy was administered to 50% Group I and to 92% Group II patients. Five-year event-free survival (EFS) and overall survival (OS) were 77% and 89%, respectively. Survival rates were influenced by tumor size (EFS 92% and 56% for size < or = and > 5 cm, respectively) and local invasiveness, not by surgical margins. No metastatic relapses occurred in Group I < or = 5 cm patients, while the outcome was poor for T2B patients (EFS 41%) due to a high rate of metastatic relapse. Our study was unable to assess the role of adjuvant treatments in grossly-resected SS, but identified a subset of low-risk patients (IRS Group I, size < or = 5 cm), for which the omission of adjuvant chemotherapy could be suggested, and a subset of high-risk patients (T2B), who need treatment intensification.

Adolescent↗

PubMed1992

Recognition of heterogeneous lymphokine-activated killer (LAK) receptors on Kaposi's sarcoma cells, endothelial cells, and monocytes/macrophages: evidence of distinct LAK-cell antigen on Kaposi's sarcoma cells--potential for use of LAK cells for immunotherapy.

The purpose of this study was to determine the potential use of lymphokine-activated killer (LAK) cells against Kaposi's sarcoma (KS) cells. We used chromium release cold-target inhibition assay for understanding the expression of heterogeneous LAK-cell antigens (Ags) on KS cells, endothelial cells (ECs), and monocytes/macrophages (M phi) which could allow for the utilization of LAK-cell immunotherapy in KS without side effects. Our data show that (i) all three cell types express the CD18 Ag of LFA-1 or Leu-CAM, (ii) rare KS cells from eyes cannot cold target-inhibit ECs, (iii) KS cells express a distinct LAK-cell Ag, which we have called LAK-KS Ag, and (iv) LAK-KS Ag allows for cold-target inhibition between different KS cells. The identification of LAK-KS Ag and a monoclonal antibody capable of inhibiting lysis of ECs and M phi without obstructing LAK-KS Ag would be important.

Antigens, CD↗

PubMed1982

The structure of the Rous sarcoma virus glycoprotein complex: in vitro phenotypic mixing of rous sarcoma virus.

Gp 85 the major envelope glycoprotein of Rous sarcoma virus can be released from intact by virus treatment with 2-mercaptoethanol. Attempts were made to reassociate released gp 85 to 2-mercaptoethanol treated virus. In order to study the biological activity and to analyse the reaction product with biochemical methods gp 85 from a subgroup different from the recipient virus was used. Successful in vitro phenotypic mixing could be shown. The biochemical analysis, however, revealed that no reassociation of gp 85 and gp 35 could be obtained. The biological activity was due to a strong association of whole gp 85-gp 35 molecules derived from the gp 85 preparation to the recipient virus. These molecules were present as a minor contamination in the gp 85 preparation.

Avian Leukosis Virus↗

PubMed1995

[Kaposi sarcoma in Caucasian women. Clinical, chemical laboratory and endocrinologic studies in 8 women with HIV-associated or classical Kaposi sarcoma].

Classic and HIV-associated Kaposi's sarcoma (KS) are predominantly found in male Caucasians. It is unclear why KS is so rare in women. At the Department of Dermatology, University of Frankfurt, epidemic KS was diagnosed in 299/751 (40%) male and 5/72 (18%) female HIV-infected patients. To detect common parameters regarding immunodeficiency, hormonal disturbances, abnormalities in clinical course, or sexual practices, data of eight women with KS (five HIV+, three HIV-) were compared. In HIV+ women KS is more aggressive than in HIV- women and more aggressive than in HIV+ men. Early and frequent visceral involvement and no preference for the lower extremities are found. Compared to HIV- women with KS, HIV+ women are generally younger (mean age 38 vs 71 years) and significantly immunodeficient (reduced absolute CD4 cell count and CD4/CD8 ratio). All women with KS investigated for sexual hormones (7/8) showed abnormalities: 7/7 had low oestrogens, 4/6 low LH and 3/5 low progesterone. Controls (n = 11, HIV+ without KS) showed a clear trend for higher serum levels of sexual hormones, but the difference was not significant. Although different reasons for low levels of oestrogens (drug abuse, marasmus, menopause) must be considered, the lack of oestrogens seems to be a common finding in HIV+ and HIV- women with KS. There was no correlation between sexual practices (anal or oral-faecal contacts) and the manifestation or aggressiveness of KS.

Acquired Immunodeficiency Syndrome↗

PubMed1984

It is Rous sarcoma virus protein P12 and not P19 that binds tightly to Rous sarcoma virus RNA.

The interactions between Rous Sarcoma virus (RSV) RNA and the viral proteins in the virus have been analysed by Sen & Todaro (1977) using ultraviolet light irradiation; they showed that the major protein ultraviolet light cross-linked to the viral RNA was P19 as identified by polyacrylamide gel electrophoresis. We report here that it is not viral protein P19 but P12 that binds tightly to RSV RNA upon ultraviolet light irradiation of the virus. Therefore, the binding sites of the viral protein along RSV RNA that we have characterized previously should be correctly attributed now to P12 and not P19.

Avian Sarcoma Viruses↗

PubMed1984

Cytoskeletal changes induced by two avian sarcoma viruses: UR2 and Rous sarcoma virus.

UR2-transformed cells were examined by immunofluorescence and compared to control cells and cells transformed by Rous Sarcoma Virus (RSV). Actin and tubulin which are normally depolymerized in RSV-transformed cells appeared to be unaffected by UR2 transformation. Cell surface fibronectin which is normally lost from RSV-infected cells, appears more abundantly on UR2-transformed cells than on normal cells. Vinculin was shown to be in adhesion plaques in UR2-transformed cells as well as in control fibroblasts but diffuse in the cytoplasm of RSV-transformed cells. Polyacrylamide gel electrophoresis of [35S]methionine-labeled fibronectin and vinculin immunoprecipitated from lysates of normal and transformed cells indicated that cell associated fibronectin synthesized during the labeling period is reduced by 60% in RSV-transformed cells but occurs in normal amounts in UR2-transformed cells. However, immunoprecipitation of radiolabeled fibronectin released in supernatant fluids of normal and transformed cells showed a decreased amount of fibronectin in fluids from UR2-transformed cells, but a considerable increase in the medium from RSV-infected cells as compared to uninfected cultures. These data suggest that more fibronectin binds to the surface of UR2-transformed cells then to normal cells, but is readily released from RSV-transformed cells. Vinculin was reduced by about 50% of normal levels in both RSV- and UR2-transformed cells. Immunofluorescence studies using antibody to virion structural proteins (gag) show that the nuclei of UR2-transformed cells are not fluorescent. This indicates a cytoplasmic location or membrane association for p68ros, the transforming protein of UR2, which contains gag determinants. Overall, these data suggest that changes in the major cytoskeletal proteins of fibroblasts are not essential for the neoplastic properties of cells but are rather a phenotypic expression of transformation, since UR2, which causes tumors in vivo, induces only minor cytoskeletal alterations of cells transformed in vitro.

Actins↗

PubMed1985

Mitomycin C (MCC) in advanced soft tissue sarcoma: a phase II study of the EORTC Soft Tissue and Bone Sarcoma Group.

Mitomycin C at a dose of 12 mg/m2 i.v. q 3 weeks was administered to 34 patients with measurable progressive advanced soft tissue sarcomas. No objective response was observed although in one of the 12 patients with overall stabilisation of disease a partial response was reported in lung lesions. The side-effects observed in this group of patients were generally mild. On the basis of this result the application of mitomycin C in this disease cannot be recommended.

Adult↗

PubMed1990

Ifosfamide plus doxorubicin in previously untreated patients with advanced soft tissue sarcoma. The EORTC Soft Tissue and Bone Sarcoma Group.

The objective of this phase II trial was to assess the therapeutic activity and toxicity of doxorubicin plus ifosfamide in previously untreated patients with advanced soft tissue sarcoma. Treatment was doxorubicin 50 mg/m2 followed by a 24 h infusion of ifosfamide 5 g/m2 plus mesna 2.5 g/m2 repeated every 3 weeks until disease progression or unacceptable toxicity occurred. Of 203 patients entered, 175 were evaluable for response. The response rate was 35% (95% CI 28-42%), with 9% of the patients achieving a complete remission and 26% a partial remission. The median time to progression was 29 weeks for all evaluable patients, and 67, 40 and 28 weeks for complete and partial responders and patients with stable disease, respectively. The median duration of survival was 58 weeks. Myelosuppression was the dose-limiting toxicity, resulting in leukopenia (WHO grade 3 and 4) in 73% of evaluable treatment courses. Other side-effects were rare and usually well manageable.

Adolescent↗

PubMed1993

Grading of soft tissue sarcomas: experience of the EORTC Soft Tissue and Bone Sarcoma Group.

A practical grading system for soft tissue sarcomas was developed, based on 282 eligible patients entered in an EORTC adjuvant clinical trial. The primary tumours in this trial had to be adequately treated. Histopathological parameters, which appeared significant in two preceding studies, were tested. These parameters were differentiation of the tumour, presence and amount of necrosis, the presence and amount of myxoid areas and the number of mitoses. In addition, the size of the tumour was also analysed. The quantitative data (mitotic count and size of the tumour) were not a priori grouped, but were divided into categories based on the results of the statistical analysis. Based on a multivariate analysis only mitotic count, the presence or absence of necrosis and the size of the tumour were significantly correlated with the duration of survival or the time to distant metastases. Of these parameters, the mitotic count was the most important.

Adolescent↗

PubMed1995

Ewing's sarcoma of the ribs. A report from the cooperative Ewing's sarcoma study.

31 patients with primary Ewing's sarcoma of the ribs were treated according to the protocols of CESS 81, CESS 86P and CESS 86. The results of treatment were reviewed and analysed. 24 patients presented with localised disease and 7 with regional disease. 20 of 24 localised cases and 6 of 7 regional cases underwent tumour resection. All but 2 localised cases received irradiation. The cumulative relapse-free survival (RFS) rate of 31 patients was 61% at 12.8 years. Patients with poor prognosis had tumour of the upper ribs (P = 0.0338), the posterior component of the ribs (P = 0.0597), or regional disease (P = 0.0001). Tumour size, existence of pleural effusion, type of the surgical margin and response to chemotherapy were not significant prognostic factors. Most of the localised cases could be controlled by combined treatment, but in regional cases prognosis remained poor.

Adolescent↗