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PubMed1979

Detection of cancer-associated antigen(s) in urine of sarcoma patients.

Tumor-associated antigens were demonstrated in concentrated and dialyzed urine of several sarcoma patients with large tumor burden. The antigens were detected by complement fixation using autologous and allogeneic sera from sarcoma patients. The antigenic activity in three patients who were studied sequentially disappeared after surgical ablation of tumor. In two of these three patients, the antigenic activity reappeared before tumor recurrence. The reactivity of the sarcoma sera to the urine could be abolished by absorption of the sera with human sarcoma cells but not by normal human liver cells, which indicates that the same antigen was present in the urine and on biopsy-obtained sarcoma cells. Urine from cancer patients with high tumor burden may be useful as a source of tumor-associated antigen. Further studies on the presence of these antigens in urine of sarcoma patients may lead to a method for detecting subclinical tumor recurrence.

Adult↗
PubMed1989

Lung resection for metastatic sarcomas: total survival from primary treatment.

The results of surgical management of 63 cases of pulmonary metastases from bone and soft tissue sarcomas, admitted at the Istituto Nazionale Tumori of Milan, between 1970 and 1987, are reviewed in this paper. To estimate the relative impact of metastasectomy on the overall performance of treatment, survival curves were calculated from the time of first thoracotomy, as well as from the initial treatment of primary sarcoma. In the present series, total actuarial survival at 10 years was 37% for osteosarcoma, 27% for soft tissue sarcomas, and 24% for the other bone sarcomas, with a median survival of 48, 56, and 36 months, respectively. Five-year survival from the first pulmonary resection was influenced by the number of metastases and the length of the first disease-free interval only in osteosarcoma, while in soft tissue sarcomas a major untoward factor was represented by local recurrence at the site of the primary tumor. These data support the concept of pulmonary metastasectomy as effective salvage therapy for radically treated sarcomas; this management can rescue a significant proportion of all relapsed patients.

Adolescent↗
PubMed1994

Bone scintigraphy in nonsurgically treated Ewing's sarcoma at diagnosis and follow-up: prognostic information of the primary tumor site.

In order to detect skeletal metastases in patients with Ewing's sarcoma, bone scanning is commonly used. However, little information is available about the scintigraphic aspects of the primary Ewing's sarcoma during non-surgical treatment and follow-up. We studied retrospectively the significance of bone scintigraphic findings at the primary tumor site of 58 patients with a Ewing's sarcoma. These patients had chemotherapy and radiotherapy. At presentation 53/58 patients showed an increased tracer uptake at the primary tumor site while 5 patients with a pelvic or sacral bone localization had a normal scan. Bone scans made during treatment and more than 2 years thereafter in the 32 eligible patients demonstrated three patterns. In 16 patients the hot spot disappeared and no local tumor recurrence was encountered. In the other 16 patients the high uptake at the primary tumor site either persisted or diminished first to a normal uptake after a median period of 18 months (range 12-36 months) and returned again to a high uptake within 6-12 months. In these patients local Ewing's sarcoma was still present in 13, while in the other 3 cases a benign disorder (fracture, ectopic bone formation) was the underlying cause. These findings suggest that in non-surgically treated Ewing's sarcoma persisting increased tracer uptake or its recurrence is highly suspicious for the presence of Ewing's sarcoma, while bone scans becoming negative and remaining so for more than 12 months suggest the absence of local tumor.

Bone Neoplasms↗
PubMed2004

Inverse correlation of secreted frizzled-related protein 4 and beta-catenin expression in endometrial stromal sarcomas.

Endometrial stromal sarcomas are rare uterine tumours. Whereas the histology and immunohistochemistry of these tumours are well documented, almost nothing is known about the molecular mechanisms involved in their pathogenesis. To characterize the genes altered in these malignancies, a genome-wide cDNA library was generated by suppression subtractive hybridization and a set of differentially expressed clones was isolated. These were then used to produce custom-spotted cDNA arrays. Genes deregulated in endometrial stromal sarcomas were identified by cDNA array hybridization and were confirmed by quantitative real-time PCR analyses and in situ hybridization. Following cDNA array analysis, more than 300 genes deregulated in endometrial stromal sarcoma were selected and sequenced. Among the most significantly deregulated genes were those of secreted frizzled-related proteins (SFRPs), in particular secreted frizzled-related protein 4 (SFRP4). SFRPs are putative modulators of the Wnt-signalling pathway and play a role in different cellular events including cell proliferation. Compared with normal endometrium, the expression of SFRP4 was decreased in both low-grade endometrial stromal sarcoma (ESS; n = 10) and undifferentiated endometrial sarcoma (UES; n = 4), being lower in the latter more aggressive form. These results were verified on paraffin wax-embedded tissue by quantitative real-time PCR analysis and in situ hybridization. Furthermore, the expression of beta-catenin, an important component of the Wnt-signalling pathway, was regulated in an opposite manner to SFRP4, being particularly increased in undifferentiated sarcomas. The activation of the Wnt-signalling pathway was additionally supported by the immunohistochemical demonstration that beta-catenin was translocated to the nucleus in UES. SFRP4 may therefore be a putative tumour suppressor involved in deregulation of the Wnt pathway and in the pathogenesis of ESS and UES.

Cytoskeletal Proteins↗
PubMed2006

Proteomic signatures corresponding to histological classification and grading of soft-tissue sarcomas.

We performed a global protein expression study on soft-tissue sarcoma in order to develop novel diagnostic biomarkers and allow molecular classification. 2-D difference gel electrophoresis was used to generate the global protein expression profiles of 80 soft-tissue sarcoma samples with seven different histological backgrounds. We found that 67 protein spots distinguished the subtypes of soft-tissue sarcoma. Hierarchical clustering with these 67 protein spots resulted in the grouping of all 80 sarcoma samples corresponding to the histological classification. We found that the expression pattern of tropomyosin isoforms was different in conventional and pleomorphic leiomyosarcomas. We also identified five proteins, including alpha-1-antitrypsin, alpha-actinin 1, HSP27, and elongation factor 2, that could differentiate between malignant fibrous histiocytomas and leiomyosarcomas in grade III into low-risk and high-risk groups, which differed significantly with respect to survival. These results establish proteomics as a powerful tool to develop novel biomarkers for diagnosis and molecular classification of soft-tissue sarcomas. Identification of proteins associated with survival in grade III sarcoma will allow delineation of a high-risk group that may benefit from adjuvant therapy and the exclusion of low-risk patients in whom additional therapies are unlikely to exhibit clinical benefit.

Biomarkers↗
PubMed1988

Soft-tissue sarcoma: initial characteristics and prognostic factors in patients with and without metastatic disease.

Five hundred and sixty-five patients with soft-tissue sarcoma were admitted to Memorial Sloan-Kettering Cancer Center from July 1, 1982 to July 1, 1985. Clinical and pathologic factors were analyzed to identify initial characteristics and to determine factors associated with prognosis and the development of metastasis. In decreasing order of frequency, the most common sites of primary tumor were the extremity (51.1%), retroperitoneum/viscera (28.8%), trunk (15.9%), head and neck (3.7%) and breast (0.4%). The most common histologic types were liposarcoma (21.4%), malignant fibrous histiocytoma (20.2%), leiomyosarcoma (20.0%), fibrosarcoma (11.0%), and tendosynovial sarcoma (9.6%). One hundred and twenty-eight patients (22.7%) had metastases in a median follow-up period of 19 months. Metastasis was more common in patients with retroperitoneal and visceral sarcomas than in patients with extremity sarcomas. Patients with leiomyosarcomas were more likely to develop metastases than those with other histologic types. Fibrosarcoma and liposarcomas were the least likely to develop metastases in this time frame. Tumors greater than 5 cm in diameter occurred more frequently in patients with metastases. Actuarial survival was related to the site of primary tumor and the histologic type and grade of malignancy. Multivariate analysis indicated that patients with low-grade sarcomas, extremity sarcomas, and fibrosarcomas and patients without metastatic disease demonstrated significantly improved survival. In patients with metastases, disease-free interval (less than 365 or greater than or equal to 365 days) was significantly related to overall survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMedDate not supplied

Molecular determinants of soft tissue sarcoma proliferation.

Soft tissue sarcoma is an extremely rare malignant disease that includes more than 15 distinct histologic subtypes. While all share a propensity for metastasis to the lungs, the clinical presentation and pattern of spread for the specific subtypes are remarkably viable. Little is known about the etiology of soft tissue sarcoma other than several well described epidemiological associations between ionizing and other toxic agents and several of the soft tissue sarcoma histologic subtypes. The key to understanding the etiologic factors driving soft tissue sarcoma proliferation and dissemination lies in understanding the molecular mechanisms underlying these oncologic processes. Progress in this regard has been difficult because of the rarity of this disease. This report reviews the current state of knowledge for three of the most important considerations involving the molecular etiology of soft tissue sarcoma: growth factors and their receptors, nuclear and cytoplasmic oncogenes, and tumor suppressor genes. As we learn more about these molecular mechanisms leading to proliferation and dissemination of soft tissue sarcoma, molecularly based genetic therapies will become a reality for this all too devastating, albeit rare, disease.

Cell Division↗
PubMed1994

KP-1: not a specific marker. Staining of 137 sarcomas, 48 lymphomas, 28 carcinomas, 7 malignant melanomas and 8 cystosarcoma phyllodes.

This study documents the reactions of the monoclonal antibody KP-1, which detects histiocytes in paraffin sections, with 137 sarcomas, 48 lymphomas, 28 carcinomas, 7 malignant melanomas and 8 cystosarcoma phyllodes. The soft tissue sarcomas had been previously immunophenotyped. Positive staining was obtained in all categories of sarcoma except clear-cell sarcomas. Most categories of sarcoma showed staining in less than 10% of tumour cells although a minority of leiomyosarcomas showed more extensive staining. Five of 7 malignant melanomas were also positive while all lymphomas and carcinomas were negative. We conclude that KP-1 positivity is not helpful in supporting the histiocytic origin of a tumour and is of limited value in the differential diagnosis of soft tissue sarcomas or their separation from other categories of malignancy.

Antigens, CD↗
PubMed1986

Localization of human sarcoma with radiolabeled monoclonal antibody. A preliminary study.

The early localization of recurrent or metastatic sarcoma remains a challenging clinical problem. 125I-labeled monoclonal antibody (Mab) 19-24, produced in our laboratories against a human malignant fibrous histiocytoma, has been evaluated for detection of locally recurrent or metastatic disease in selected sarcoma patients. In vitro testing indicated various degrees of positive Mab reactivity with most sarcoma types, and low but significant reactivity with some nonsarcoma tumors and several normal tissues, including liver. The iodine-labeled Mab had an immunoreactivity of 90% and a high binding constant (8.1 X 10(9) M-1). Biodistribution studies of radioisotope in sarcoma patients showed rapid clearance of radiolabeled from the blood and uptake in tumor deposits, liver, and spleen. A differential in radioactivity kinetics between liver and tumor was also found. Serial patient scanning determined optimal imaging time to be between 24 and 48 h after i.v. infusion of the radiolabeled Mab. Analysis of tissues obtained during surgery (including a dual antibody-label study using a nonspecific Mab) showed selective localization of the Mab into the sarcoma deposits. Radiolabeled Mab shows potential as a clinically useful tool for localization of sarcoma deposits.

Adult↗
PubMed1975

Plasma membrane structures of medulloblastoma and cerebellar sarcoma.

Three medulloblastomas and 1 cerebellar sarcoma were studied on their plasma membrane structures. The average number of membrane particles per mum2 plasma membrane was 710 on face A and 70 on face B of medulloblastoma and 1280 on face A and 160 on face B of cerebellar sarcoma. The membrane particles were often aggregated in medulloblastoma and diffusely scattered in cerebellar sarcoma. Small gap junctions were occasionally found in cerebellar sarcoma and not evident in medulloblastoma. Round membrane protrusions, about 0.5-0.6 mu in diameter and provided with several small depressions on their foot, were often observed in region of narrow perinuclear cytoplasm of cerebellar sarcoma and different in structure from cytoplasmic processes. The present series is too limited in number to allow a definite conclusion, but indicates that the plasma membrane structures are different in medulloblastoma and cerebellar sarcoma.

Cell Membrane↗
PubMed1996

Evaluation of P-glycoprotein expression in soft tissue sarcomas of the extremities.

Soft tissue sarcomas comprise a heterogeneous group of mesenchymal tumors accounting for less than one-percent of adult neoplasms. In the last few years, the use of adjuvant chemotherapy has been proposed for the treatment of these lesions in order to obtain a better systemic control, but its usefulness is still controversial. In this study, we evaluated whether P-glycoprotein, a membrane protein strictly associated with multidrug resistance, is overexpressed in soft tissue sarcomas. By using human multidrug resistant sarcoma cell lines as controls, we analyzed P-glycoprotein expression in 34 primary and in 23 relapsed soft tissue sarcomas of the extremities. Overexpression of P-glycoprotein was found in 6 out of 34 primaries (18%) and in 8 out of 23 relapses (35%). In particular, in malignant fibrous histiocytoma, the most frequent soft tissue sarcoma of adults, P-glycoprotein overexpression was found in 23% of primary untreated cases, in agreement with the reported relapse rate of this tumor after surgery and chemotherapy. These data suggest that, in soft tissue sarcomas, overexpression of P-glycoprotein may be of prognostic value and that the assessment of P-glycoprotein expression may be useful for the design of chemotherapy protocols.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Neurogenic potential of Ewing's sarcoma cells.

We investigated the capacity of eight well-characterized Ewing's sarcoma cell lines to differentiate towards a neural phenotype. Ewing's sarcoma cells expressed the neuroectoderm-associated antigens such as nerve growth factor (NGF) receptor, N-CAM (6H7 and Leu-19) and Leu-7. Ewing's sarcoma cells also exhibited the potential for neural differentiation at the mRNA level; neuron-specific medium- and low-sized filament (NF-M and NF-L) expression was induced by dibutyryladenosine cyclic monophosphate. The pattern of expression of NF-L obtained by using alternative polyadenylation sites in Ewing's sarcoma cells differed from that in peripheral primitive neuroectodermal tumour (PNET) cells, and was similar to that in undifferentiated neural tissues. Furthermore, the NGF receptors detected by immunohistochemistry were found to be non-functional as assayed by c-fos induction with NGF treatment. The results indicate that Ewing's sarcoma cells maintain a primitive phenotype and have the potential to differentiate into a neural phenotype, indicating that Ewing's sarcoma is distinct from PNET.

Bone Neoplasms↗
PubMed1992

Expression of functional Y1 receptors for neuropeptide Y in human Ewing's sarcoma cell lines.

In the human Ewing's sarcoma cell line WE-68, saturation analysis using 3H-labelled neuropeptide Y ([3H]NPY) as the radioligand disclosed a homogeneous population of binding sites with a dissociation constant (Kd) of 4.5 nM and maximal binding capacity (B(max)) of 712 fmol/mg cell protein. Besides the WE-68 cell line, ten other human Ewing's sarcoma cell lines (FM-62, HS-80, HT-78, HT-M1-78, NT-68, RM-82, RS-63, VH-64, WE-M1-68, WE-M2-68) were also found to display NPY receptors with Kd varying from 3.5 nM to 10.7 nM and B(max) = 247-3744 fmol/mg cell protein. NPY, its natural analogues and the Y1-receptor-specific peptide ligand [Leu31,Pro34]NPY inhibited [3H]NPY binding in the potency order: [Leu31,Pro34]NPY greater than or equal to human NPY greater than or equal to peptide YY (PYY) greater than salmon pancreatic polypeptide (PP) greater than human PP greater than porcine NPY13-36 much greater than NPY22-36. In the Ewing's sarcoma cell lines NPY provoked inhibition of forskolin-stimulated cyclic AMP formation by up to 98%. Pertussis toxin alleviated the cyclic-AMP-inhibitory response to NPY. In isolated Ewing's sarcoma plasma membranes pertussis toxin [32P]ADP-ribosylated a 41-kDa protein. The ability of NPY and analogues to inhibit cyclic AMP accumulation paralleled their potencies in displacing radioligand binding. By contrast, a cell line derived from an atypical form of Ewing's sarcoma did not express specific and functional NPY receptors. These results demonstrate that conventional Ewing's sarcoma cells possess Gi-protein-coupled NPY receptors of the Y1 type, which upon interaction with NPY, PYY, and PP mediate inhibition of cyclic AMP generation.

Adult↗
PubMed1996

Expression of multidrug-resistance-associated protein gene in human soft-tissue sarcomas.

We examined the mRNA expression of the multidrug- resistance-associated protein gene (MRP) in soft-tissue sarcomas and compared it with the expression of the multidrug resistance gene (MDR1), using the reverse transcriptase/polymerase chain reaction. We investigate 39 samples from 33 cases of soft-tissue sarcomas (11 liposarcomas, 9 malignant fibrous histiocytomas, 6 leiomyosarcomas, 4 malignant schwannomas, 3 fibrosarcomas, 3 synovial sarcomas, and 3 epithelioid sarcomas) and 7 benign soft-tissue tumors. All samples were obtained prior to chemotherapy. An expression of MRP mRNA was noted in 56% of soft-tissue sarcoma specimens. The co-expression of MRP and MDR1 was recognized in 15 samples (38%) (5/11 liposarcomas, 5/9 malignant fibrous histiocytomas, 3/6 leiomyosarcomas, 2/3 fibrosarcomas) and significantly correlated with histological grade (P=0.0165). A positive and significant correlation was found between MRP and MDR1 expression in soft-tissue sarcomas(P=0.0013). In benign soft-tissue tumors, 1 chemodectoma and 1 neurothekeoma showed low MRP expression; however, no case showed co-expression of MRP and MDR1.

ATP-Binding Cassette Transporters↗
PubMed1992

Factor-XIIIa-expressing dermal dendrocytes in Kaposi's sarcoma. A comparison between classical and immunosuppression-associated types.

The histogenetic origin of Kaposi's sarcoma is a matter of controversy, with recent reports claiming it to derive from the factor-XIIIa-positive dermal dendrocyte rather than endothelial cells. We investigated the potential role of factor-XIIIa-positive dermal dendrocytes in the genesis of both classical (endemic) and immunosuppression-associated Kaposi's sarcoma. Thirteen cases of classical and 16 cases of immunosuppression (mostly AIDS)-associated Kaposi's sarcoma were immunostained with antibodies to factor XIIIa and to the blood-group antigen H, recognizing endothelial cells. Factor-XIIIa-positive cells were consistently antigen-H-negative and represented only a small percentage (usually less than 10%) of the proliferative cells. Their relative density tended to be decreased in immunosuppression-associated Kaposi's sarcoma when compared with that of the classical form. These results do not support the view that dermal dendrocytes may be the cells of origin of Kaposi's sarcoma; conversely, their decreased density in cases of immunosuppression-associated Kaposi's sarcoma could be related to immunosuppression and may account for more rapid tumour growth.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Microsatellite instability in sarcomas.

BACKGROUND: Microsatellite instability (MIN) has been studied in a variety of carcinomas and gynecologic sarcomas, but never in musculoskeletal sarcomas. METHODS: We evaluated 16 skeletal and soft tissue sarcomas at nine genetic loci from chromosomal regions 1q, 5q, 7q, 12p, 13q, 17p, 19q, and two at 11p--all potential regions of interest regarding musculoskeletal sarcomas. RESULTS: MIN was identified at one or more loci in seven of the cancers studied (44%). Three tumors had more than one locus with MIN and one tumor, a high-grade osteogenic sarcoma, had five of nine loci positive for MIN. CONCLUSION: These results indicate that musculoskeletal sarcomas show instability in areas inside and outside the loci of known oncogenes. Areas of mismatch repair, as heralded by MIN, may contribute to the vast heterogeneity of these neoplasms.

Adolescent↗
PubMed1997

Elevation of glutathione and related enzyme activities in high-grade and metastatic extremity soft tissue sarcoma.

BACKGROUND: Glutathione is a free radical scavenger implicated in the chemoresistance of certain tumors. As treatment with chemotherapy has added little to improved survival in adult soft tissue sarcoma and little is known concerning the mechanisms of chemoresistance in sarcoma, we studied concentrations of glutathione (nmol/mg protein) and activities of gamma-glutamylcysteine synthetase (GCS; nmol/mg protein/h) and gamma-glutamyl transpeptidase (GGTP; U/mg protein) in extremity soft tissue sarcoma. METHODS AND RESULTS: Tumor specimens (n = 65) were frozen in liquid nitrogen at the time of resection. Fourteen low-grade tumors, 40 high-grade tumors, and 11 pulmonary metastases were analyzed. Glutathione concentrations and GGTP activity were significantly lower in low-grade (3.97 +/- 0.7 nmol/mg protein and 1.07 +/- 0.2 U/mg protein) than in high-grade (8.98 +/- 1.2 nmol/mg protein, p < 0.001; 2.10 +/- 0.4 U/mg protein, p < 0.002) tumors and pulmonary metastases (10.05 +/- 1.8 nmol/mg protein, p < 0.008; 3.14 +/- 2.8 U/mg protein, p < 0.04). While GCS activity was lower in low-grade (0.81 +/- 0.3 nmol/mg protein/h) than high-grade (1.49 +/- 0.5 nmol/mg protein/h) tumors and pulmonary metastases (1.03 +/- 0.2 nmol/mg protein/h), these differences were not significant. In those patients with a high-grade tumor presenting with a local recurrence, glutathione levels were higher in those patients who had received preoperative doxorubicin-based chemotherapy (9.25 +/- 1.7 nmol/mg protein; n = 7) than in those who had no preoperative chemotherapy (4.71 +/- 3.1 nmol/mg protein; n = 4, p = 0.08). CONCLUSIONS: In extremity soft tissue sarcoma, glutathione concentration and GGTP activity are significantly elevated in patients with high-grade and metastatic sarcomas. In addition, there is a trend for increased glutathione levels in tumors previously exposed to doxorubicin-based chemotherapy. Glutathione may play a role in soft tissue sarcoma chemoresistance.

Adolescent↗
PubMed1997

Epithelioid sarcoma: clinical behavior and prognostic factors of survival.

BACKGROUND: Epithelioid sarcoma is a rare histologic subtype of sarcoma. The clinical behavior and prognostic factors influencing survival in this disease are examined. METHODS: A review of clinicopathologic features of patients with epithelioid sarcoma prospectively followed between July 1982 and July 1995 at Memorial Sloan-Kettering Cancer Center was performed. Kaplan-Meier and log-rank analysis were used. RESULTS: Eleven men (69%) and five women (31%) were treated during this period. Mean age at diagnosis was 33 years, and length of symptoms before diagnosis was 18 months. Tumors presented in the trunk in 44% of patients, the lower extremity in 31%, and the upper extremity in 25%. Median follow-up time was 45 months. At least one local recurrence was experienced by 69% of patients. Metastases to regional lymph nodes during the course of the disease developed in 44% of patients and to the lungs in 44%. Median survival was 88.8 months, with a 66% 5-year survival rate. Pulmonary metastasis was correlated with decreased survival. CONCLUSIONS: A delay in diagnosis of epithelioid sarcoma is common. Epithelioid sarcoma differs from other sarcoma subtypes in propensity for nodal spread and local recurrence. Careful follow-up evaluating local recurrence, nodal spread, and pulmonary metastases is warranted.

Adolescent↗