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PubMed1995

CD3- large granular lymphocytes recognize a heat-inducible immunogenic determinant associated with the 72-kD heat shock protein on human sarcoma cells.

Traditionally, heat shock proteins (HSPs) are believed to be located intracellularly, where they perform a variety of chaperoning functions. Recently, evidence has accumulated that some tumor cells express HSPs on the cell surface. The present study confirms this finding and correlates HSP72 cell surface expression, induced by nonlethal heat shock, with an increased sensitivity to interleukin-2-stimulated CD3-natural killer (NK) cells. After nonlethal heat shock, a monoclonal antibody directed against the major heat-inducible 72-kD HSP (HSP72) stains the cell surface of sarcoma cells (ie, Ewing's sarcoma cells or osteosarcoma cells) but not that of normal cells (ie, peripheral blood lymphocytes, fibroblasts, phytohemagglutin-stimulated blasts, B-lymphoblastoid cell lines) or of mammary carcinoma cell line MX-1 carcinoma cells. In this study, we show for the first time a correlation of HSP72 cell surface expression with an increased susceptibility to lysis by NK effector cells. This finding is supported by the following points: (1) HLA-disparate effector cells show similar, elevated lysis of HSP72+ heat-treated sarcoma cells; (2) CD(3-) NK cells, but not CD3+ cytotoxic T lymphocytes, are responsible for the recognition of heat-shocked sarcoma cells; (3) by antibody-blocking studies, an immunogenic HSP72 determinant, which is expressed selectively on the cell surface of heat-treated sarcoma cells could be correlated with NK recognition; (4) the reported phenomenon is independent of a heat-induced, transient downregulation of major histocompatibility complex (MHC) class-I expression; and (5) blocking of MHC class-I-restricted recognition, using either MHC class-I-specific monoclonal antibody W6/32 on the target cells or alpha/beta T-cell receptor monoclonal antibody WT31 on effector cells, also has no inhibitory effect on the lysis of HSP72+ tumor cells. Finally, our in vitro data might have further clinical implications with respect to HSP72 as a stress-inducible, sarcoma-specific NK recognition structure.

Antibodies, Monoclonal↗

PubMed1994

Oncologic outcomes of primary bone sarcomas of the pelvis.

Although many studies have been performed for evaluation of surgical techniques and surgical morbidity in cases of primary pelvic sarcoma, few have addressed the long term oncologic outcomes for these patients. Therefore, the outcome of 41 patients with primary pelvic bone sarcomas were followed for 2-13 years (average, 6 years; median, 5 years). There were 18 chondrosarcomas (15 low grade and 3 high grade tumors), 11 osteosarcomas (1 low grade and 10 high grade tumors), 5 high grade malignant fibrous histiocytomas of bone, 5 Ewing's sarcomas, 1 undifferentiated sarcoma, and 1 low grade angiosarcoma of bone. Fifteen of the 17 patients with low grade tumors survived (88%), whereas only 6 of the 24 patients with high grade tumors survived (25%). Local disease recurred in 1 of the 24 (4%) patients with high grade tumors and in none of the patients with low grade tumors. Reoperations for complications were required in 33% of the patients. A difference could not be demonstrated in the quality of surgical margins or in the surgical morbidity, patient survival, and rate of local recurrence between patients treated with hemipelvectomy (8) and those treated with pelvic resection (32). Patients with low grade pelvic sarcomas have a good prognosis after pelvic resection, but those with high grade sarcomas continue to have a poor prognosis.

Adolescent↗

PubMed1993

Different types and different prognosis-study of 310 uterine sarcomas.

Three hundred and ten cases of uterine sarcomas, among them, according to pathology: LMS (Leiomyosarcoma)--117, MMS (Mixed mesodermal sarcoma)--62, ESS (Endometrial stromal sarcoma)--56, CS (Carcinosarcoma)--27, RBMS (Rhabdomyosarcoma)--18 and other sarcomas--30, were retrospectively evaluated at the Maria Skłodowska-Curie Memorial Cancer Center between 1950 and 1985. These mesodermal tumors were divided into uterine corpus sarcomas (295) and the rarely occurring uterine cervix sarcomas. As the main modality of treatment 307 patients underwent surgery. Almost all patients received adjuvant radiotherapy but 51 cases of LMS. Overall 5-year survival was 34.5% and in particular subgroups the survivals were as follows: the best, 52% in LMS; lower, 30% in ESS; poor survival about 20% in CS and MMS. In spite of low curability in the majority of subgroups except LMS, the cases of CS with primary site in uterine cervix distinguished itself with better results. No significant survival advantage was found for surgery plus radiotherapy in LMS with low grade mitotic activity, (10 mitoses/10 HPF) compared with surgery alone (63% and 54%). These cases seem to have better prognosis in LMS with high grade mitotic activity (10 mitoses/10 HPF) and do not require adjuvant radiotherapy.

Adult↗

PubMed1995

DNA content and morphological parameters in synovial sarcoma and synovioma.

By using image analysis technique with 6 normal synovial tissue specimens as controls, nuclear DNA content and morphological parameters in specimens from 51 synovial sarcomas and 15 synovioma were examined quantitatively. The DNA content in synovial sarcoma and synovioma was significantly different (P < 0.01), and that of synovioma and normal synovial tissue was also different (P < 0.05). Morphological parameters including nuclear areas and perimeters differed significantly among the above three groups (P < 0.01). There was no correlation between the DNA content of synovial sarcoma and its histologic type (P > 0.05), but the DNA content greatly differed between its higher and lower differentiated grade in each type (P < 0.01). The DNA content in synovial sarcoma IIA stage, according to Enneking's staging system was lower than that in IIB, IIIA and IIIB (P < 0.05). The 5-year survival rate of synovial sarcoma with diploid/nearly diploid (D/ND) pattern was higher than that of aneuploid (AN) pattern (P = 0.028). The study suggests that analysis of the DNA content and morphological parameters of tumor cells is helpful in the diagnosis and pathologic grading of synovial sarcoma. It also provides a guide to clinical operation and estimation of the prognosis. Although synovioma is usually a well-differentiated and benign lesion, this investigation also suggested that increased DNA content may be an indication of poor prognosis for this neoplasm.

Adolescent↗

PubMed1996

Chromosomal translocation t(X;18) in human synovial sarcomas analyzed by fluorescence in situ hybridization using paraffin-embedded tissue.

Synovial sarcoma is characterized cytogenetically by translocation t(X;18)(p11.2;q11.2). In this study, 28 cases that had been diagnosed initially as synovial sarcoma, including 2 fibrosarcomas, and 1 leiomyosarcoma were collected and examined for translocation t(X;18) on paraffin-embedded tissues by fluorescence in situ hybridization (FISH). Of the synovial sarcomas, 25 showed findings consistent with translocation t(X;18) with an additional copy signal for the total probe of X and 18 chromosomes. The other three cases, as well as the two fibrosarcomas and the leiomyosarcoma, did not show this translocation. One (case 26) of three negative cases was diagnosed finally as leiomyosarcoma and another (case 27) as malignant peripheral nerve sheath tumor from histological and immunohistochemical analysis. Thus, in all, 25 (96%) of 26 synovial sarcomas showed findings consistent with translocation t(X;18). In summary, translocation t(X;18) is a chromosomal aberration specific for synovial sarcoma. The fluorescence in situ hybridization technique can be used even on cells from paraffin-embedded tissues, and is a useful diagnostic aid for synovial sarcoma.

Adolescent↗

PubMed1996

Detection and sequence analysis of a new herpesvirus-like agent in AIDS and non-AIDS Kaposi's sarcoma in Taiwan.

A new herpesvirus-like DNA sequence (KSHV) has been recently identified in Kaposi's sarcoma from acquired immunodeficiency syndrome (AIDS) and non-AIDS patients. In order to verify the role of this new viral agent in Taiwan, a series of Kaposi's sarcoma specimens obtained from AIDS and non-AIDS patients in three medical centers representing different geographic locations of Taiwan were surveyed. A total of seven specimens from AIDS patients and 22 specimens from non-AIDS patients were tested for the presence of this herpesvirus-like agent by polymerase chain reaction (PCR) using the published Kaposi's sarcoma 330-233 primers. The tumor DNA was also tested for cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpes-virus type 6 (HHV-6). The Kaposi's sarcoma specimens from AIDS and non-AIDS patients were positive for KSHV except in one case. Only occasional specimens were positive for CMV and EBV, with a slightly higher positive rate for HHV-6 in AIDS and non-AIDS patients. Cloning and sequence analysis of the PCR products from two cases of Kaposi's sarcoma (one each for AIDS and non-AIDS) revealed only minor differences in this DNA sequence, as compared with the published data from north America. These results further support the assumption that this new KSHV is strongly associated with Kaposi's sarcoma in AIDS and non-AIDS patients in Taiwan.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Ultrastructural evidence for divergent and alternating differentiations in spindle cell sarcoma xenografts.

Seven spindle cell sarcomas, 5 poorly differentiated ones and 2 moderately well differentiated ones, were established on nude mice and long term passaging was done. Sarcoma strains were analysed electron microscopically in an attempt to get further insight in spindle cell sarcoma differentiation pathways. Ultrastructurally, the tumours were classified as malignant peripheral nerve sheath tumour (3/7), leiomyosarcoma (2/7), rhabdomyosarcoma (1/7), and spindle cell sarcoma not otherwise classifiable (1/7). Undifferentiated tumour cells including fibroblastoid ones predominated in most xenografts, whereas cells harbouring cytoplasmic specificities tended to be few in number. Nevertheless, divergent differentiations exhibiting unusual double or triple patterns could be documented ultrastructurally in 12/30 xenografts with juxtaposed myomatous as well as nerve sheath-like cells and, in addition, histiocytoid (MFH-like) elements in 3 of the xenografts. Moreover, sarcoma strains alternated fine structural constellations in the course of passaging, whereby different phenotypes, myomatous, nerve sheath-like, unspecific, or mixed ones, succeeded one another. These findings pursue recent immunohistochemical data on multidirectional sarcoma differentiation by means of electron microscopy. They, furthermore, fit well into the concept of multipotential stem cells as progenitors in mesenchymal differentiation and suggest microenvironment to play a modifying role in the expression of cell differentiation.

Adult↗

PubMed1997

Uterine sarcoma: a clinicopathological study of 93 cases.

OBJECTIVE: To evaluate the clinical outcome of patients suffering from primary uterine sarcoma diagnosed and treated in our Hospital. SETTING: Department of Gynecologic Surgery/Gynecologic Oncology, Hospital Universitario Materno-Infantil Vall d'Hebron de Barcelona, Barcelona, Spain. SUBJECTS AND METHODS: A retrospective review from 1967 to 1995 of clinical and pathological characteristics of 93 patients with primary uterine sarcoma was done. Patients were staged using the 1988 FIGO histological classification for uterine cancer. Clinical features, type of surgery, adjuvant therapy, recurrences, distant metastasis, and survival were recorded. RESULTS: Our study included three main histologic types: 44 patients with leiomyosarcoma, 26 patients with endometrial stromal sarcoma, and 18 patients with mixed Müllerian sarcomas. The mean age for all patients was 54.8 years, and the most common symptom was vaginal bleeding. Other clinicopathological features were examined. Although surgery was the most frequent treatment, adjuvant therapies have been analyzed and discussed. The overall three-year survival rate was 67.9% and the overall five-year survival rate was 64.5%. We found statistical differences (p < 0.001) between the stage I survival rate and other stage survival rates. CONCLUSIONS: Uterine sarcoma is an uncommon neoplasia diagnosed in the 6th decade of life. Leiomyosarcoma is the most frequent histologic type (47.3%). Stage I uterine sarcoma has a better prognosis than other stages.

Adult↗

PubMed1997

The future of sarcoma treatment.

The last two decades have shown exciting and dramatic improvements in the management of osteogenic sarcoma, while progress in soft tissue sarcomas has lagged behind considerably. Osteogenic sarcoma treatment has been a model of multidisciplinary collaboration. Orthopedic surgeons working together with medical and pediatric oncologists have improved disease-free survival while improving limb salvage rates and limb function. In contrast, the care of soft tissue sarcoma remains fragmented among many disciplines and specialties. Medical and pediatric oncologists, radiation oncologists, and a myriad of surgical specialists are all involved in the care of soft tissue sarcomas, and significant treatment (usually surgical) often occurs before referral to a center. Significant variation in managment leads to considerable difficulty in assessing the effects of treatment on outcome. Improvement in soft tissue sarcoma management will occur only when physicians recognize the need to centralize care to appropriate physicians within referral centers where patients can be treated on standardized cooperative protocols.

Antineoplastic Agents↗

PubMed1998

Synovial sarcoma of the parotid gland. A case report with clinicopathological analysis and review of the literature.

Primary sarcomas of the major salivary glands are exceptionally uncommon. Synovial sarcoma is a distinctive neoplasm which usually arises in the extremities in the region of joints. Although synovial sarcomas arising in the head and neck region are well described, tumours actually originating in and around the major salivary glands are exceedingly rare, with few cases reported in the literature. We report a synovial sarcoma in the right parotid gland of a 67-year-old man. The literature pertaining to salivary gland sarcomas and synovial sarcoma of the head and neck region is reviewed.

Aged↗

PubMed1995

Antitumor activity of antifolate inhibitors of thymidylate and purine synthesis in human soft tissue sarcoma cell lines with intrinsic resistance to methotrexate.

We examined the antitumor effects of two antifolate inhibitors of thymidylate synthesis, N-(5-[N-(3, 4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino ]-2-theno yl-L-glutamic acid (D1694; Tomudex) and 1843U89 as well as a folate-based inhibitor of purine synthesis, 5, 10-dideazatetrahydrofolic acid (DDATHF) on human soft tissue sarcoma cell lines having intrinsic resistance to methotrexate (MTX) due to impaired accumulation of polyglutamates of MTX (HS-16 and HS-42 cells) and to increased levels of dihydrofolate reductase and thymidylate synthase activity (HS-18 cells). Growth inhibition studies showed that ED50 values for D1694 and 1843U89 after a 24-h exposure were 11-19-fold and 22-222-fold lower, respectively, than those for MTX in HT-1080, a MTX-sensitive cell line, and the three MTX-resistant cell lines. In contrast, DDATHF was less cytotoxic than MTX in both the MTX-sensitive and the three resistant sarcoma cell lines. Uptake of D1694, 1843U89, or DDATHF was 2.5-4.5-fold higher than MTX in these sarcoma cell lines. However, D1694 and 1843U89, unlike MTX, accumulate in HS-16 and HS-42 cells as polyglutamate forms, reaching 70% of the total intracellular drug level after 24 h. DDATHF polyglutamates (9.4-24%) were less in the same cell lines. Much lower Km values for D1694 and 1843U89 as compared to MTX for folylpolyglutamate synthase were measured in the sarcoma cell lines, with Vmax values equal to or slightly higher than those obtained with MTX. D1694 and 1843U89 are significantly more cytotoxic than MTX in intrinsically MTX-resistant sarcoma cell lines as a result of extensive formation of polyglutamates. These two thymidylate synthase inhibitors should be evaluated in patients with soft tissue sarcomas.

Antimetabolites, Antineoplastic↗

PubMed1998

Simultaneous expression of Fas and nonfunctional Fas ligand in Ewing's sarcoma.

Fas-Fas ligand interactions play a central role in the regulation of the immune response. Fas ligand expression by tumors has been implicated in the abrogation of the host antitumor response by killing of Fas-positive effector lymphocytes. We have studied the presence and functional status of Fas and Fas ligand in Ewing's sarcoma. All Ewing's sarcoma cell lines tested expressed Fas on their surface. Three of the cell lines were readily killed after ligation of the Fas receptor. Four additional cell lines exhibited Fas-mediated apoptosis after preincubation with IFN-gamma and/or cycloheximide, whereas two cell lines were resistant to Fas-mediated killing. With regard to Fas ligand, all cell lines examined were positive for protein by immunoblot, and specificity was confirmed by reverse transcription-PCR. However, using flow cytometric analysis, Fas ligand could only be detected in Ewing's sarcoma cells after permeabilization. Furthermore, the cell lines were not capable of inducing apoptosis of Fas-sensitive Jurkat cells. In addition, Ewing's sarcoma cell lines were able to serve as stimulators for the generation of cytotoxic effector lymphocytes and were susceptible to lysis by them. Therefore, Fas ligand is expressed in Ewing's sarcoma but is not functional, suggesting that Ewing's sarcoma is a potential target for immunotherapy.

Apoptosis↗

PubMed1993

Adult type (nonembryonal) soft tissue sarcomas in childhood.

Nonembryonal soft tissue sarcomas are rare in childhood. We report our experience from a series of 28 patients treated at this centre, whose treatment was based on primary surgical resection. No patient required limb amputation. Anatomical distribution and histological subtypes differed from the adult sarcoma population. A total of 79 percent of the sarcomas were classified as high grade. Six patients (21%) developed local recurrence, and 6 patients (21%) developed distant recurrence, including 3 patients (11%) who developed both. Median follow-up was 57 months. Actuarial 5 years survival was 82%, which compares favorably with the 5 year survival of adults with high grade soft tissue sarcomas treated at this centre (63%) and with the survival of children with embryonal sarcomas treated by chemotherapy.

Adolescent↗

PubMed1984

Diagnosis of soft tissue sarcomas.

Based on a review of 752 cases coded as soft tissue sarcomas, histologic features were analyzed for a differential diagnosis, dividing the sarcomas in the first diagnostic step into purely descriptive groups, regardless of biologic behavior: spindle cell, small cell, pleomorphic and myxoid varieties. The tumor categories mainly discussed in order were fibrosarcoma, leiomyosarcoma, malignant schwannoma, synovial sarcoma, malignant fibrous histiocytoma, embryonal and alveolar rhabdomyosarcoma, malignant neuroepithelioma , extraskeletal Ewing's sarcoma, and myxoid and other types of liposarcoma. The discussion was focused on the problems we were facing often in the histologic diagnosis of these tumors, emphasizing in particular those microscopic features which were helpful in differential diagnosis. Principal clinical features, important for an accurate diagnosis, were added to the histopathologic considerations in each item, together with prognosis of all these Japanese patients, regardless of the stages. Other benign and malignant lesions confused occasionally with the soft tissue sarcomas were also listed. With the aid of electron microscopy and immunohistochemistry, sometimes each differentiating feature can be identified but these methods are not always contributory to a diagnosis. Routine light microscopy with or without standard histochemical techniques remains essential to avoid pitfalls when attempting to diagnose the tumor.

Chondrosarcoma↗

PubMed2000

Nonrhabdomyosarcoma soft tissue sarcomas in children. The Mayo Clinic experience.

Eighty-six children to 18 years of age were treated for nonrhabdomyosarcoma soft tissue sarcomas of the trunk and extremities. Synovial sarcoma (31), fibrosarcoma (13), malignant fibrous histiocytoma (11), epithelioid sarcoma (10), and clear cell sarcoma (7) were the most common diagnoses. Four patients presented with metastatic disease. A high percentage of patients presented after biopsy by the referring physician, although this could not be shown to affect outcome. Patients were treated with wide removal of the tumor when possible, with judicious use of adjuvant radiation, or with chemotherapy in selected cases. Mean followup was 11 years. Five- and 10-year survival was 92% and 84%, respectively. Tumors larger than 5 cm were associated with a worse prognosis. When compared with published data in adults, the prognosis of primary, localized nonrhabdomyosarcoma soft tissue sarcomas in children appears to be more favorable.

Adolescent↗

PubMed2002

Immunohistochemical staining for KIT (CD117) in soft tissue sarcomas is very limited in distribution.

We performed immunohistochemical analysis for KIT in 365 soft tissue sarcomas. Most tumors evaluated were completely negative for KIT, including all cases of leiomyosarcoma, rhabdomyosarcoma, myxofibrosarcoma, liposarcoma, solitary fibrous tumor, synovial sarcoma, dermatofibrosarcoma protuberans, schwannoma, malignant peripheral nerve sheath tumor, clear cell sarcoma, low-grade endometrial stromal sarcoma, and follicular dendritic cell sarcoma. Tumors showing occasional immunoreactivity for KIT included extraskeletal myxoid chondrosarcoma (2/20), Ewing sarcoma/malignant primitive peripheral neuroectodermal tumor (4/20), melanotic schwannoma (3/5), metastatic melanoma (4/20), and angiosarcoma (5/20). In most cases, staining for KIT was focal. Rare tumor cells showing KIT positivity were identified in a small number of other tumors. This study demonstrates very limited expression of KIT in soft tissue tumors other than gastrointestinal stromal tumors and underscores the discriminatory value of KIT immunohistochemical analysis for differential diagnosis. As some of these findings differ markedly from previous reports, it is evident again that variations in immunohistochemical technique can lead to major discrepancies in positive staining. Since treatment eligibility for selective tyrosine kinase inhibitors such as STI571 hinges on positive immunostaining, standardization and reproducibility of meaningful results are critically important.

Chondrosarcoma↗

PubMed1999

[High-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) for refractory bone and soft tissue sarcomas].

High-dose chemotherapy with autologous peripheral blood stem cell transplantation was administered to 10 patients with refractory bone and soft tissue sarcoma (2 patients with primitive neuroectodermal tumor, 4 patients with Ewing's sarcoma, 3 patients with synovial sarcoma and one patient with osteosarcoma). Busulfan 4 mg/kg x 4, melphalan 140 mg/m2 and thiotepa 200 mg/m2 x 3 were used in the high-dose chemotherapy. Complications related to the treatment were limited to one patient who developed hepatic veno-occlusive disease, no serious complications were seen in the other patients. Four patients died of their disease, one patient was alive with the disease and 5 patients were alive with no evidence of disease. The prognosis for non-resectable primitive neuroectodermal tumor and Ewing's sarcoma is said to be very poor. However, there are some patients in whom the disease is kept in remission by high-dose chemotherapy with autologous peripheral blood stem cell transplantation, so this therapy may be a possible substitute for radical operation. With spindle cell sarcomas, the efficacy of this treatment was temporary, so it will be necessary to investigate frequent high-dose chemotherapy and to change the high-dose chemotherapy regimen.

Adolescent↗

PubMed1976

Identification and subcellular localization of a sarcoma-associated antigen(s) in a human cell line.

The present investigation was designed to demonstrate and identify the subcellular localization of sarcoma-associated antigen(s) (TAA) in an established human neurogenic sarcoma line (T cell line). Indirect immunofluorescence was used to screen sera from patients with sarcoma, nonsarcoma neoplasias, and from presumably normal blood bank donors. The positive sera were submitted to a series of absorptions to remove possible nonspecific cross-reacting antibodies. The target cells were then studied with electron microscopy, utilizing the indirect immunoperoxidase technique to determine the subcellular localization of the sarcoma-associated antigen(s). Findings indicate that sarcoma-bearing patients have circulating antisarcoma antibodies directed to antigen(s) localized at the surface membrane of T cells. These antibodies pertain to the IgM or IgG immunoglobulin class. The exact nature of the sarcoma-associated antigen(s) identified in this study is not known at the present time. However, the results obtained strongly suggest that these substances may represent a new type of tumor-associated antigen(s).

Antibodies, Neoplasm↗