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Epithelioid sarcoma and synovial sarcoma in the same knee.

A patient who had had a synovial sarcoma removed from the soft tissues adjacent to his knee subsequently developed an epithelioid sarcoma on the opposite side of the same joint. The epithelioid sarcoma metastasized to lymph nodes, invaded blood vessels and produced death 16 years after it was first discovered. The unique association of these two tumors may be an interesting coincidence or may have some relevance to the histogenesis of epithelioid sarcoma.

Adult↗

Prognostic factors in retroperitoneal sarcoma: a multivariate analysis of a series of 165 patients of the French Cancer Center Federation Sarcoma Group.

BACKGROUND: Surgery is the main prognostic factor in retroperitoneal sarcoma. However, despite progress, surgery alone is rarely curative, and analysis of the causes of failures and of other prognostic factors are warranted to ascertain treatment orientations. METHODS: Data of patients treated from 1.80 to 12.94 for primary retroperitoneal sarcoma were extracted from the French Federation of Cancer Centers Sarcoma Group registry. Univariate and multivariate analysis were performed for initial local control and for local and general outcome. One hundred sixty-five patients (median age, 54 years; range, 16--82 years) were identified. Median tumor size was 15 cm (range, 2--70 cm); 31% of tumors presented with neurovascular or bone involvement. Liposarcoma, leiomyosarcoma, and malignant fibrous histiocytoma represented 66% of the tumors. Eighty-four percent of the tumors were of high or intermediate grade. Twenty patients had initial metastases. Multimodality treatment included surgery (150 patients), radiotherapy (92 patients), and chemotherapy (77 patients). Complete excision was achieved in 94 of 145 nonmetastatic patients. Median follow-up was 47 months (range, 3--160 months). RESULTS: Actuarial overall 5-year survival rate (median) was 46% (51 months). The main prognostic factors for survival were initial metastases and surgery, which represented the major treatment-linked factor. High-grade of tumors affected local recurrence, metastatic recurrence, and survival. Adjuvant radiotherapy was significantly associated with reduced local recurrence. Various evolutive patterns were observed with histologic subtypes. CONCLUSIONS: Aggressive surgery remains mandatory in retroperitoneal sarcoma, but a randomized trial is needed to evaluate the place of radiotherapy for local control.

Adolescent↗

Primary pulmonary sarcomas with features of monophasic synovial sarcoma: a clinicopathological, immunohistochemical, and ultrastructural study of 25 cases.

We present 25 cases of a primary pulmonary sarcoma bearing histological, immunohistochemical, and ultrastructural features indistinguishable from those of monophasic synovial sarcoma of soft tissue. The patients were 11 men and 14 women between the ages of 16 and 77 years. Clinically, the most common symptoms were chest pain, cough, shortness of breath, and hemoptysis. The lesions involved all lung segments. Grossly, they varied in size from 0.6 to 20 cm and were described as soft to rubbery tumors with areas of necrosis and hemorrhage, some with cystic changes. Two lesions involved the bronchial wall and in one case the tumor was described as encircling the bronchial tree. Histologically, all of the lesions were characterized by an atypical spindle cell proliferation with a solid growth pattern. Areas of myxoid, neural, hemangiopericytic, and epithelial-like growth pattern were observed. Mitoses, necrosis, and hemorrhage were seen in all lesions in varying proportions. Immunohistochemical studies for epithelial membrane antigen (EMA) and keratin showed strong focal positivity in 25 of 25 and 23 of 25 lesions, respectively. Immunohistochemical study for vimentin showed diffuse strong positivity in all lesions. Other immunostains, including desmin, smooth muscle actin, and S-100 protein, were negative. Electron microscopy in three cases showed spindle cells with elongated nuclei containing abundant cytoplasmic rough endoplasmic reticulum and well developed desmosome type intercellular junctions. Follow-up information ranging from 2 to 20 years was obtained in 18 patients. Six patients died of their tumors, whereas four patients died of unrelated causes without evidence of recurrence or metastases. Eight patients were alive with disease (recurrence and/or metastases) from 1 to 7 years after diagnosis. Four patients were alive and well without evidence of recurrence or metastases from 2 to 20 years (mean follow-up, 12.5 years). The present group of lesions appears to constitute a distinctive and as yet previously undescribed primary sarcoma of the lung, which probably represents the visceral counterpart of monophasic synovial sarcoma of soft tissue in a pulmonary location. Because of their distinctive biology these lesions should be distinguished from a variety of primary and metastatic malignancies of the lung.

Adolescent↗

Location of envelope-specific and sarcoma-specific oligonucleotides on RNA of Schmidt-Ruppin Rous sarcoma virus.

Envelope-specific and sarcoma-specific nucleotide sequences have been located within the 10,000 nucleotides of the RNA of nondefective Schmidt-Ruppin Rous sarcoma virus (nd SR). For this purpose, about 30 RNase-T1-resistant oligonucleotides were ordered relative to the 3'-poly(A) terminus of the RNA, to construct an oligonucleotide map of the nd SR RNA. A cluster of seven envelope-specific oligonucleotides, identified by their absence from an otherwise very similar oligonucleotide map of an envelop-defective deletion mutant (which lacks the major viral glycoprotein), mapped at a distance of 2800-5000 nucleotides from the poly(A) end of nd SR RNA. A cluster of two sarcoma-specific oligonucleotides, identified by their absence from an otherwise nearly identical oligonucleotide map of a transformation-defective deletion mutant, mapped at a distance of 1000-2000 nucleotides from the poly(A) end of nd SR RNA. The oligonucleotide maps of nd SR and of the two deletion mutants were the same from the poly(A) end up to 650 nucleotides and included one terminal oligonucleotid, termed C, which is found in all avian tumor viruses tested so far. A possible gene order consistent with our data suggests that sarcoma-specific nucleotide sequences map between envelope-specific nucleotide sequences and the poly(A) end of the RNA.

Avian Sarcoma Viruses↗

Synovial sarcoma, histologically mimicking primitive neuroectodermal tumor/Ewing's sarcoma at distant sites.

We report a case of synovial sarcoma (SS) showing unusual histology at distant sites. A 47-year-old man was aware of a tumor on the sole of his left foot. After preoperative chemotherapy with a diagnosis of SS, wide excision was performed. During postoperative chemotherapy, multiple tumorous lesions developed in the bone (including the whole spine) and both lungs. The patient died 1 year later. Histologically, the excised tumor of the foot showed a biphasic cellular pattern typical of SS, whereas at autopsy the bone and lung lesions were composed only of undifferentiated small round cells with cytoplasmic fibrillar processes. Homer-Wright rosettes were also observed. Immunohistochemically, 80% of the bone and lung tumor cells expressed MIC2 protein homogeneously. To clarify whether the bone and lung round cell tumors were metastatic lesions or second malignancies, especially primary primitive neuroectodermal tumor (PNET)/Ewing's sarcoma (ES), we performed reverse transcription-polymerase chain reaction (RT-PCR) analysis of tumor type-specific fusion gene transcripts. The SYT/SSX fusion transcript was identified in both the foot and lung lesions, whereas the EWS/FLI1 transcript was not detected in either lesion. Therefore, we concluded that the multiple bone and lung tumors were poorly differentiated metastatic tumors, which arose from the SS of the foot. We also conclude that the identification of chimeric fusion transcripts can be successfully applied to poorly differentiated sarcomas and will help in the differential diagnosis of tumors that cannot be distinguished by conventional morphological examinations. Also, it should be remembered that cytoplasmic staining for MIC2 protein may occur in sarcomas other than PNET/ES.

12E7 Antigen↗

Effect of recombinant human interleukin 2 on the growth of a BALB/c sarcoma induced by Moloney murine sarcoma virus.

The effect of in vivo administration of recombinant interleukin 2 (rIL2) on the growth of a primary female BALB/c sarcoma induced by Moloney murine sarcoma virus (M-MSV) was studied. Although low-dose administration of (6,000 JU/mouse x 14 days) rIL2 had no effect on the growth of the tumors, high-dose (15,000-80,000 JU/mouse x 14 days) intraperitoneal inoculation of rIL2 induced tumor regression, dose-dependently. Tumors in mice which received 80,000 JU/mouse/day of rIL2 regressed completely 2 weeks after the initiation of treatment. The survival rates of the treated groups were significantly higher than those of the control group. A time course experiment disclosed that the effect of rIL2 was restricted only to the group in which rIL2 treatment started 8 days after the inoculation of M-MSV. The cytotoxic activity of regional lymph node lymphocytes from rIL2-treated mice was demonstrated against primary culture of M-MSV-induced sarcoma but not against syngeneic tumor induced by methylcholanthrene (Meth A). The effect of rIL2 was partially blocked by the administration of anti-IL2 receptor antibody. Immunohistochemical examination revealed that infiltration of Thy1.2+Lyt1+2- (helper/inducer subset) lymphocytes into the tumor tissue was prominent in mice which received high-dose rIL2. The results indicated that IL2 induced regression of M-MSV-induced sarcoma mainly through activation of IL2-receptor-positive helper T cells in the tumor tissues and of killer cells in the draining lymph nodes.

Animals↗

Structure and functions of the Kirsten murine sarcoma virus genome: molecular cloning of biologically active Kirsten murine sarcoma virus DNA.

The unintegrated closed circular form of viral DNA prepared from NIH3T3 cells infected with Kirsten murine sarcoma virus was cloned into bacterial plasmid pBR322. The closed circular DNA, which consisted of two different-sized populations, was enriched from the virus-infected cells, linearized with BamHI, and inserted into pBR322 DNA. Four different recombinant DNAs (clones 2, 4, 6, and 7) were obtained, and a physical map of each was constructed by using various restriction enzymes. Clone 4 DNA had the largest insertion, corresponding to a complete copy of the linear DNA. This suggested that this insertion contained two copies of the 0.55-kilobase pair long terminal redundant sequence. Clone 2 and clone 6 insertion DNAs had deletions of 0.2 and 0.5 kilobase pair, respectively, which mapped near the right end (3' side of viral RNA) of the linear DNA. Clone 7 DNA appeared to have a deletion of a single copy of the large terminal redundant sequence. Transfection of BALB3T3 cells with the clone 4 DNA insertion showed that this DNA had transforming activity. The efficiency of transfection with clone 4 Kirsten murine sarcoma virus DNA was enhanced eightfold by inserting EcoRI-cleaved viral DNA into the EcoRI site of pBR322. The EcoRI-inserted DNA produced foci with single-hit kinetics, suggesting that a single molecule of Kirsten murine sarcoma virus DNA can induce transformation. Results of transfections with EcoRI-inserted Kirsten murine sarcoma virus DNA cleaved with various restriction enzymes suggested that the first 3.3-kilobase pair region at the left end of the linear DNA is important for the initiation of transformation or maintenance of transformation or both.

Animals↗

Rous sarcoma virus does not induce sarcoma in early chick embryos by lack of the v-src gene expression.

The Schmidt-Ruppin or the B77 strain of Rous sarcoma virus (RSV) was inoculated into limb buds of 4.5-days-old avian embryos. No sarcoma but blister formation was observed in those RSV-inoculated embryos. Protein kinase activity of pp60v-src in RSV-inoculated embryos, even in the site of virus inoculation, was the same as that in mock-infected embryos. This indicated that the expression of the v-src gene did not attain superiority over that of the c-src gene in RSV-inoculated embryos. The v-src gene was detected in every DNA from tissues of RSV-inoculated embryos but not in DNAs from tissues of RSV-inoculated chicken except for the DNA from Rous sarcoma. Those results confirmed that the lack of sarcoma induction in early avian embryos by RSV was due to the lack of the expression of the v-src gene which was present in the target cells.

Animals↗

Significance of surgical margin on the prognosis of patients with Ewing's sarcoma. A report from the Cooperative Ewing's Sarcoma Study.

BACKGROUND: There is little information regarding an adequate surgical margin for local control of Ewing's sarcoma. METHODS: Two hundred and forty-four patients (PTS) with Ewing's sarcoma who were registered in the Cooperative Ewing's Sarcoma Studies underwent surgical treatment. Ninety-four PTS underwent definitive surgery (surgery alone), 131 PTS received postoperative irradiation, and 19 PTS received preoperative irradiation. The surgical margins were distributed as follows: radical, 29 PTS; wide, 148 PTS; marginal, 39 PTS; and intralesional, 28 PTS. The impact of the surgical margin on the treatment outcome of PTS was analyzed statistically. RESULTS: The local or combined (local recurrence and systemic metastasis) relapse rate after surgery with or without irradiation was significantly lower compared with that after definitive irradiation (irradiation alone) (7% vs. 31%, P < 0.0001). The local or combined relapse rate after complete resection (radical or wide margin) with or without irradiation was less compared with that after incomplete resection (marginal or intralesional margin) with or without irradiation (5% vs. 12% P = 0.0455). The local or combined relapse rate did not greatly decreased after irradiation after incomplete surgery (from 14% to 12%). In both groups of good (viable tumor cells < 10%) and poor (viable cells > or = 10%) histologic response, the difference in systemic or combined relapse rate between patients undergoing complete and incomplete surgery was not significant. The 10-year overall survival of the PTS for each of the margins was distributed as follows: radical, 58%; wide, 65%; marginal, 61%; and intralesional, 71% (P = not significant). CONCLUSIONS: Surgery in patients with Ewing's sarcoma adds to the safety of local control. Under the current treatment regimen with intensive chemotherapy and irradiation, complete resection of the tumor appears capable of decreasing the risk of local recurrence.

Adolescent↗

A cell culture, chromosomal and quantitative DNA analysis of a metastatic epithelioid sarcoma. Deletion 1p, a possible primary chromosomal abnormality in epithelioid sarcoma.

The chromosomal banding pattern and the in vitro growth characteristics of a metastatic epithelioid sarcoma are described. The cultured tumor cells retained growth characteristics as well as ultrastructural and immunohistochemical properties similar to the cells of the primary tumor. Cytogenetic analysis revealed a modal range in the diploid-hypodiploid region, a finding which was corroborated by quantitative DNA determinations of both the primary tumor and a lymph node metastasis. Fourteen different marker chromosomes were identified. The most frequent clonal rearrangement was a 1p-marker resulting from a short arm terminal deletion, i.e., del (1) (p21-22). A similar 1p- marker has previously been observed in an established epithelioid sarcoma cell line. The finding of an apparently identical 1p-marker in two of two analyzed epithelioid sarcomas suggests that this rearrangement may be a primary cytogenetic abnormality in epithelioid sarcoma. An elevated ras p21 expression was demonstrated using immunohistochemical methods. The possible involvement of the N-ras gene and/or a tumor suppressor in the 1p deletion is considered.

Chromosome Aberrations↗

[Histological grading of soft tissue sarcomas: stratification of G2-sarcomas in low- or high-grade malignant tumors].

Histological grading according to one of the proven systems, e.g. that of the FFCCS, leads to the definition of different prognostic risk groups. Prerequisite is a precise typing of the tumors, if necessary by immunohistochemical and molecular-pathological methods. The therapeutic decision is dependent on the presence either of a low- or high-grade malignant tumor: With low-grade sarcomas surgery has priority, with high grade tumors usually chemo- and/or radiotherapy are indicated. With the latter, also better therapeutic response is reported. Therefore, conversion of a 3-grade into a 2-grade system has to be carried out by including the tumor localization as prognostic parameter. Thereby, the large group of G2-sarcomas with intermediate malignancy can be stratified. Superficial G2-sarcomas are considered to be low grade and deep G2-sarcomas high grade malignant. Immunohistochemical staining of tumor cell nuclei with Ki67/MIB1 allows a more standardized and precise grading. The ultimate aim, not to define risk groups, but to predict the prognosis for individual patients, possibly could be reached someday by molecular diagnostic methods.

Humans↗

Ultrasound findings in uterine mixed müllerian sarcomas and endometrial stromal sarcomas.

Sonographic findings in five cases of mixed mullerian tumors and two cases of endometrial stromal sarcoma which were evaluated before surgery for staging are reviewed. Assessment of myometrial invasion was in agreement with surgical findings in five cases; in the two other cases invasion was overestimated. The echo pattern of these tumors presented some peculiarities. In five patients, four with mixed mullerian tumors and one with endometrial stromal sarcoma, a heterogenous pattern with high-intensity and hypoechoic areas scattered in the myometrium was seen. In the other two cases the sonographic picture was indistinguishable from that of leiomyomas. Sonography is an accurate imaging technique for preoperative staging of uterine sarcomas. If an heterogenous echo pattern of the uterus as described is found at sonography, sarcoma should be suspected and laparotomy performed urgently.

Adult↗

The transforming proteins of Rous sarcoma virus, Harvey sarcoma virus and Abelson virus contain tightly bound lipid.

We have found that the transforming proteins of Rous sarcoma virus, Harvey sarcoma virus and Abelson virus all contain tightly bound lipid. This modification could play a role in the binding of these proteins to cellular membranes. The lipid associated with p60src, the transforming protein of Rous sarcoma virus, is located in the NH2-terminal domain of the polypeptide. This is the region of the protein that has been shown previously to participate in binding the protein to membranes. Two mature forms of p21, the transforming protein of Harvey sarcoma virus, contain lipid. Lipid is not, however, associated with newly synthesized p21. While mature p60src and p21 are bound to cellular membranes, the newly synthesized forms of these proteins are not. The posttranslational addition of lipid may therefore be the means by which these proteins acquire an affinity for membranes.

Abelson murine leukemia virus↗

N-(phosphonacetyl)-L-aspartate (PALA) in advanced soft tissue sarcoma: a phase II trial of the EORTC soft tissue sarcoma group.

Thirty-six patients with measurable or evaluable advanced soft tissue sarcoma were entered in a phase II trial with PALA. Among the 27 evaluable patients, 15 were men, the median age was 55 yr (16-69) and the median performance status (Karnofsky) was 80 (50-100). Most patients had leiomyosarcoma (8), liposarcoma (3), neurofibrosarcoma (3), synovial cell sarcoma (3), or undifferentiated sarcoma (3). Indicator lesions consisted essentially of lung metastases (21) and/or soft tissue lesions (14). All patients had received prior chemotherapy with 1-5 regimens and 6 had achieved objective response with these previous treatments. PALA was given as a 60-min i.v. infusion at a daily dose of 2.5 g/m2 for two consecutive days. Courses were repeated every two weeks. A median number of 3 courses (2-17) were administered. Partial remission (greater than 50%) was obtained in one patient with a liposarcoma who had also responded to prior combination chemotherapy. This single response to PALA lasted 6 weeks from initiation of therapy. Four patients had unchanged disease after 6+ courses of PALA and 22 had progressive disease. Toxic effects were generally mild to moderate and included cutaneous toxicity (17), diarrhea (14), stomatitis (13), ocular manifestations, consisting of conjunctivitis, corneal ulceration and/or photophobia (11), nausea and vomiting (6) and, possibly, seizures (2). There was no evidence of drug-related myelosuppression. It is concluded that PALA given at the dose schedule selected for this trial has no significant antitumor activity in advanced soft tissue sarcoma previously treated with chemotherapy.

Adolescent↗

Chromosomal alterations in low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma as detected by comparative genomic hybridization.

OBJECTIVE: Endometrial stromal sarcomas (ESS) are very rare neoplasms constituting less than 0.5% of all malignant uterine tumors. The aim of the present study was to characterize the karyotypic abnormalities in these malignant mesenchymal tumors and to find specific chromosomal aberrations with eventual correlation with histologic grades. METHODS: Twelve cases of endometrial stromal sarcomas consisting of nine low-grade ESS and three undifferentiated endometrial sarcomas (UES) were investigated by comparative genomic hybridization (CGH). RESULTS: Ten of the twelve cases (83.3%) displayed chromosomal gains or losses. Deletions occurred more frequently than gains (63.4% versus 36.6%). In low-grade ESS, gains on 1, 6q, 9q, 16p, 19, 20q, 22q and losses on 2, 4q, 6, 7, 11q, 13q, 15q, 16q, 20p, X were detected. CGH with UES exhibited gains on 2q, 4q, 6q, 7p, 9q, 20q and losses on 3q, 10p, 14q. One low-grade ESS and one UES did not reveal any chromosomal aberration. CONCLUSIONS: Chromosomal aberrations in endometrial sarcomas are heterogeneous and do not clearly correlate with the histologic grades. There is no increased accumulation of aberrations from low-grade ESS to UES. Despite the karyotypic variations, chromosomal deletion on 7p was the most common finding (55.6%) in low-grade ESS and may play a role in tumor development and progression.

Chromosome Aberrations↗

[Soft tissue sarcoma in children and adolescents: experiences of the cooperative Soft Tissue Sarcoma Group Studies (CWS-81 - 96)].

The very heterogeneous group of paediatric soft tissue sarcomas account for approximately 7 % of all malignant childhood tumours. More than one half of all cases are rhabdomyosarcomas, some of the over 20 entities are very rare. The prognosis and biology of soft tissue sarcomas in children and adolescents vary greatly depending on histological subtype, the age of the patient, the primary site, the tumour size, tumour invasiveness and the extent of disease at diagnosis. Since 1981, 2918 children and adolescents with soft tissue sarcomas were treated prospectively according to the common treatment protocols of the Cooperative Soft Tissue Sarcoma Study Group (CWS-81 - 96). The known prognostic factors were used to develop a more and more detailed risk stratification. The multimodal treatment includes the use of surgery, chemotherapy and radiotherapy and should be planned by a multidisciplinary team. That way, an overall survival of nearly 70 % over all risk groups could be achieved.

Adolescent↗

[Purely mesenchymal homologous uterus sarcomas (leiomyosarcomas and endometrial stroma sarcomas) at the Zurich University Gynecologic Hospital].

From 1960 through 1983 sixty-four so-called pure mesenchymal homologous sarcomas of the uterus were observed at the Women's University Hospital Zürich. A review of the histological slides revealed that only 40 cases represented true sarcomas according to the contemporary diagnostic criteria. These were 25 leiomyosarcomas and 15 endometrial stromal sarcomas. Leiomyosarcomas: The leading symptoms in these patients are uncharacteristic abdominal pain (15/25) as well as bleeding disturbances (11/25), the latter being present with equal frequency in the pre- and post-menopause. In 7 of the 11 patients with bleeding abnormalities the diagnosis was already made on examination of curettings, in all the other patients after laparotomy only. Sixteen patients had Stage I, four Stage III and five Stage IV tumors. The treatment consisted in surgery alone (9/25), surgery combined with radiotherapy (11/25) or with chemotherapy (2/25) as well as radiotherapy alone (1/25). In two cases no therapy was undertaken because of advanced cachexia of the patients. Only three patients are still alive without recurrence 4 to 12 years after the diagnosis, all had Stage I tumors. Endometrial stromal sarcomas: In these patients bleeding abnormalities represent the leading symptom (14/15), especially postmenopausal bleeding (13/14). In all cases with vaginal bloody discharge the diagnosis was made on examination of the curettings, in a single case after laparotomy only. Eight patients had Stage I, three Stage II, three Stage III and one Stage IV tumors. The treatment consisted of surgery alone (4/15) or in combination with radiotherapy (4/15), radiotherapy alone (6/15) and chemotherapy alone (1/15).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Decrease of tyrosine-O-sulfate-containing proteins found in rat fibroblasts infected with Rous sarcoma virus or Fujinami sarcoma virus.

Our interest was aroused by the recent report by Huttner [ Huttner , W. B. (1982) Nature (London) 299, 273-276] on general sulfation of tyrosine residues of proteins in normal and malignantly transformed tissues. Here we report on the reduction of sulfation in embryonic rat fibroblasts, line 3Y1, infected with Rous sarcoma virus or Fujinami sarcoma virus. In view of the instability of tyrosine O-sulfate in strong acid, the protein sulfation was tested for after incubation with [35S]sulfate and exhaustive Pronase hydrolysis. We found in general a reduction of sulfation in transformed tissue. It was greatest in the fibroblasts permanently transformed with Rous sarcoma virus. When fibroblasts transformed by the temperature-sensitive Fujinami sarcoma virus, line ts225 -3Y1, were used for comparison of sulfation at nonpermissive and permissive temperatures, the latter showed a strong reduction. Furthermore, we tested these cells for the uptake of inorganic [35S]sulfate. Uptake appeared highly reduced in the permanently infected fibroblasts, but ts225 -3Y1 grown at permissive and nonpermissive temperatures exhibited no difference. Uptake at both temperatures was comparable to uptake by normal 3Y1 cells. A recently much investigated cell surface protein, fibronectin, was reported to be lost on malignant transformation and to contain sulfate in an undetermined location. We found that ts225 -3Y1 cells grown at permissive temperature released fibronectin that contained tyrosine O-sulfate.

Animals↗