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PubMed1994

Nuclear immunoreaction of p53 protein in soft tissue sarcomas. A possible prognostic factor.

BACKGROUND: Tumor suppressor gene p53, located on the short arm of chromosome 17, frequently mutates in various types of cancers and plays a critical role in the multiple stages of carcinogenesis. However, there is little information about the clinicopathologic significance of alterations of the p53 gene in soft tissue sarcomas (STS). METHODS: Because it is known that nuclear accumulation of p53 protein correlates closely with the presence of mutations in the p53 gene, immunohistochemical detection of this protein was performed. A polyclonal antibody (RSP-53) raised against synthetic human p53 peptide was used to detect nuclear accumulation of the protein. Pathologic specimens of 96 patients with STS were collected from the surgical pathology files of the National Cancer Center Hospital and examined. RESULTS: Nuclear accumulation of p53 protein was detected in 31 (32.3%) patients. The percentage of patients with a positive immunoreaction was high in patients with malignant schwannoma (100%), rhabdomyosarcoma (71.4%), and synovial sarcoma (50.0%), whereas it was low in patients with liposarcoma (13.6%) and 0% in those with fibrosarcoma. It was closely associated with the histologic grade of malignancy (grade 1, 12.0%; grade 2, 30.8%; grade 3, 44.4%) and the patient's age (younger than 40 years, 46.9%; 40 years of age or older, 25.0%). Both overall and metastasis-free survival rates were significantly lower for patients with a nuclear p53 immunoreaction than for those without it. CONCLUSIONS: The nuclear p53 immunoreaction is considered a marker of tumor aggressiveness and appears to be a useful prognostic factor for STS.

Adolescent↗
PubMed1987

[Analysis of liposarcoma].

Liposarcoma is one of the most common soft tissue sarcomas, ranking with rhabdomyosarcoma and malignant fibrous histiocytoma. We have treated 47 cases of liposarcoma, comprising 35 males and 12 females ranging in age from 22 to 86 years, with a median age of 56 years. The most common site of primary tumor was the thigh, the most common primary tumor stage by the UICC classification was T2, and the most common histological subtype by the WHO classification was myxoid type. Xerography, CT and angiography are useful forms of examination for diagnosis before surgery. Naked eye findings of the tumor often show a lobular or nodular growth pattern. Surgical therapy for the primary tumor, especially curative wide resection (by the method of Kawaguchi, et al.) is most effective for preventing local recurrence. Radiotherapy is not as effective as for rhabdomyosarcoma and chemotherapy should be applied for occult micro-metastases. Ten of the 47 cases died due to distant metastases and the 5 year survival rate was 76.2%.

Adult↗
PubMed1996

Translocations in solid tumours.

Specific chromosomal translocations have now been identified in a variety of solid tumour types. Recent developments in this field include the identification of novel genes involved in the t(X;18) synovial sarcoma translocation and the discovery that the high-mobility group protein gene, HMGI-C, is involved in the chromosome 12 rearrangements found in lipomas and uterine leiomyomas. These discoveries may have important implications for the strategies used in tumour diagnosis and treatment.

Humans↗
PubMed2003

Immunohistochemical analysis of Smac/DIABLO expression in human carcinomas and sarcomas.

Second mitochondria-derived activator of caspases (Smac/DIABLO) is released from mitochondria into the cytosol during apoptosis, promoting caspase activation by neutralizing the inhibition of inhibitor of apoptosis proteins (IAPs) on caspases. Alteration of apoptosis is essential for cancer development, and cancer cell death by radiation and chemotherapy is largely dependent upon apoptosis. In this study, archival tissues of 100 carcinomas and 50 sarcomas from various origins were analyzed by immunohistochemistry for the expression of Smac/DIABLO. Smac/DIABLO immunoreactivity was seen in 62 of 100 (62%) carcinomas, including 42 of 60 stomach carcinomas, 7 of 10 colorectal carcinomas, 4 of 10 lung carcinomas, 7 of 10 ovarian carcinomas, and 2 of 10 prostate carcinomas. Smac/DIABLO is expressed in 11 of 50 (22%) sarcomas, including 2 of 8 malignant schwannomas, 5 of 11 rhabdomyosarcomas, 2 of 7 malignant fibrous histiocytomas, 1 of 6 leiomyosarcomas, 0 of 8 angiosarcomas, 0 of 8 liposarcomas, and 1 of 2 Ewing's sarcomas. These data demonstrated that Smac/DIABLO expression levels vary depending on the individual cancer types. Furthermore, the present study showed that many human cancers do not express Smac/DIABLO, and suggest that lack of Smac/DIABLO expression in the cancer cells may inhibit apoptosis, thereby promoting their survival.

Apoptosis↗
PubMed2005

Distant metastasis in retroperitoneal dedifferentiated liposarcoma is rare and rapidly fatal: a clinicopathological study with emphasis on the low-grade myxofibrosarcoma-like pattern as an early sign of dedifferentiation.

The metastatic incidence of retroperitoneal dedifferentiated liposarcoma is comparatively lower than other pleomorphic sarcomas, varying widely from 1 to 18%. Low-grade dedifferentiation resembling low-grade fibrosarcoma has been recently accepted as part of the morphologic spectrum of dedifferentiated liposarcoma and was reported to have similar metastatic and survival rates to its high-grade counterpart. We sought to determine the metastatic incidence of retroperitoneal dedifferentiated liposarcoma, the clinicopathological features related to metastasis, and their postmetastatic behavior. Of all 354 retroperitoneal liposarcoma cases diagnosed at Memorial Sloan-Kettering Cancer Center during 1982-2003, we identified seven patients developing distant metastases, occurring in four females and three males, ranging from 35 to 73 years in age at presentation. They were all de novo dedifferentiated, while none of the well-differentiated liposarcoma or secondary dedifferentiated liposarcoma developed distant metastasis. Primary tumor sizes varied from 7.5 to 25 cm. All seven patients developing metastases contained >or=50% dedifferentiated elements in the primary tumor, with a predominant morphology resembling myxofibrosarcoma in five cases. The metastatic sites included the lung in four patients, somatic soft tissue in two, and liver in one. The median metastasis-free survival was 48 months, with only two patients experiencing local recurrences before developing metastasis. Six patients died of disease at median follow-up of 53 months after diagnosis and only 5 months after their first metastases. In conclusion, retroperitoneal dedifferentiated liposarcoma have a low metastatic rate, which is strongly related to de novo dedifferentiated histology that usually constitutes a prominent component of the primary tumor. Irrespective of the grade dedifferentiated liposarcoma with myxofibrosarcoma-like features should be closely monitored. Once metastases occur, they tend to follow a rapidly fatal course.

Adult↗
PubMed1976

Tumours arising in skeletal muscle in adults.

A review has been made of 30 cases of tumours arising in skeletal muscle seen over a 21-yr period (1954-74) in the Department of Pathology, Western General Hospital, Edinburgh. There were 17 females and 13 males in the series. The age range was 15 to 88 yr. The commonest site was thigh muscles (18 cases). Seven of the 14 benign tumours were myxomas: the other benign tumours included two solitary myositis ossificans, two haemangiomas and three lipomas. The three tumours which might be considered as being of borderline malignancy were two haemangiopericytomas and one desmoid tumour. There were 13 malignant tumours in the series: five fibrosarcomas, five liposarcomas, two rhabdomyosarcomas and one undifferentiated (pleomorphic) sarcoma. The average length of survival of the nine patients with malignant tumours who have died was only 15 mth. The fibrosarcomas in particular behaved in a highly malignant fashion. These 13 intramuscular sarcomas accounted for approximately 11 per cent, of all mesenchymal (non-lymphoid) sarcomas seen during the period of study.

Adolescent↗
PubMed1989

[Radiosensitivity of soft tissue sarcomas].

The correlation between the effectiveness of radiation therapy and the histology of soft tissue sarcomas was investigated. Of 31 cases with a soft tissue sarcoma of an extremity treated by conservative surgery and postoperative radiation of 3,000-6,000 cGy, local recurrence occurred in 12; 5 out of 7 synovial sarcomas, 4 of 9 MFH, one of 8 liposarcomas, none of 4 rhabdomyosarcomas and 2 of 3 others. As for the histological subtyping, the 31 soft tissue sarcomas were divided into spindle cell, pleomorphic cell, myxoid and round cell type, and recurrence rates were 75%, 33.3%, 16.7% and 0%, respectively. From the remarkable difference in recurrence rate, it was suggested that round cell and myxoid type of soft tissue sarcomas showed a high radiosensitivity compared to the spindle cell type with low sensitivity. Clarifying the degree of radiosensitivity is helpful in deciding on the management of limb salvage in soft tissue sarcomas of an extremity.

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↗
PubMed2001

Cytogenetic and molecular genetic analyses of liposarcoma and its soft tissue simulators: recognition of new variants and differential diagnosis.

Liposarcoma is one of the most common sarcomas of adults. Its differential diagnosis and accurate subclassification are often problematic; the latter is also important with regard to appropriate treatment and prognosis. We studied a series of 23 liposarcomas that had unusual or previously undescribed features and 10 liposarcoma simulators and correlated the morphologic, cytogenetic, and molecular genetic findings. We found that use of cytogenetic-molecular genetic techniques aids in the distinction between myxoid-round cell liposarcoma and their simulators, chondroid lipoma, myxoid spindle cell-pleomorphic lipoma, cellular intramuscular myxoma, and myxofibrosarcoma. Poorly differentiated forms of round cell liposarcoma lacking morphologic evidence of lipogenesis can also be diagnosed using these techniques; however, the techniques do not aid in distinguishing low-grade myxoid from high-grade round cell liposarcomas. This study also shows that retroperitoneal liposarcomas with myxoid liposarcoma-like zones are part of the morphologic spectrum of well-differentiated-dedifferentiated liposarcoma rather than true myxoid liposarcomas. Perhaps most importantly, our results provide the first molecular genetic evidence that true mixed liposarcomas (mixed well-differentiated and myxoid liposarcoma) do indeed exist. They also unequivocally demonstrate the existence of small, round cell variants of pleomorphic liposarcoma that closely simulate myxoid-round cell liposarcoma.

Adult↗
PubMed2001

[Monstrous, retroperitoneal liposarcoma--a case report].

Liposarcomas comprise about 20% of soft tissue sarcomas and occur in 14% in the retroperitoneal space originating in one third from the perirenal fat. The case of a patient with an extraordinary huge, resectable, well-differentiated retroperitoneal liposarcoma is reported. The presenting symptoms were abdominal pain and distension as well as weight gain. Magneticresonance imaging revealed a huge retroperitoneal tumor suspected of well-differentiated liposarcoma. Curative resection of the tumor could be obtained. Only 50% of all tumors are excised without residual tumor and recurrence, occurring in 90% after 10 years, is the main therapeutic challenge. Since neoadjuvant and adjuvant therapy as well as intraoperative radiotherapy failed to prove prognostic value, curative resection remains the main treatment for primary and recurrent liposarcomas.

Adipose Tissue↗
PubMed1977

A clinical and pathological staging system for soft tissue sarcomas.

A system for staging the clinical status of patients with soft tissue sarcomas is presented, based on the clinical characteristics of the primary tumor (size, extension), the involvement of lymph nodes, the presence of metastases, and the grade of the tumor. This represents the TNM system with grade of tumor (G) added. The system evolved was based on examination of 1215 cases of 13 types of soft tissues sarcomas, primarily in the extremities (fibrosarcoma, liposarcoma, etc.). Nine stages are described, and they are correlated with survival in the cases reviewed. The staging system now can be used for case evaluation for therapy determination and for intercomparison of series of patients as to incidence of different kinds of tumors, effects of treatment, and survival.

Adult↗
PubMed2005

[Giant retroperitoneal liposarcoma--case report].

Retroperitoneal liposarcomas are the most frequent soft tissue sarcomas and the second most frequent retroperitoneal tumours. They represent less then 0.1% of all human malignancies. Hereby we describe the treatment of our patient where of a 15-kg giant retroperitoneal liposarcoma was successfully removed and a local recurrence two years later was operated on as well. This was the 3rd largest retroperitoneal malignant tumor that was successfully removed according to the available literature of the last five decades. These typically symptom-free tumors usually grow extreme size before diagnosed. The "gold-standard" of treatment remains surgical total excision, but the high local recurrence rate (50-60%) hopefully can be reduced by adjuvant radio- and chemotherapy. Multidisciplinary treatment and long-time follow-up can provide as high as 40% 5-year survival rate. We summarize the recent clinical, diagnostic and therapeutic methods of this rare condition.

Humans↗
PubMed1978

Major vascular reconstruction for limb salvage in patients with soft tissue and skeletal sarcomas of the extremities.

Thirteen patients with sarcomas of the extremities have been treated with radical en bloc resection requiring vascular reconstruction as initial treatment. In one instance, vascular reconstruction failed. Eight patients are currently alive and free of disease. There were two instances of a local recurrence. Each of the remaining five patients who died had distant metastases develop, none of whom had a local recurrence. Vascular reconstruction with prosthetic bone replacement, when indicated, offers an alternative approach to the treatment of tumors which, because of attachment to major vascular structures, might be considered for radical amputation.

Bone Neoplasms↗
PubMed1993

Case report 797: "Dedifferentiated" lipoma-like liposarcoma of soft tissue with focal transformation to high-grade "sclerosing" osteosarcoma.

We have presented the first case of a lipoma-like liposarcoma of the soft tissues with high-grade malignant transformation to a high-grade osteosarcoma, the latter component of which responded well to systemic chemotherapy. With 4 months of follow-up the patient is without evidence of disseminated disease. The various types of liposarcoma are listed and several described in some detail. Of particular importance is the potential for development of a highly malignant sarcoma from a relatively indolent low-grade liposarcoma, with even osteosarcoma developing.

Aged↗
PubMed2006

Frequent amplifications and abundant expression of TRIO, NKD2, and IRX2 in soft tissue sarcomas.

Copy number gains and high-level amplifications of the short arm of chromosome 5 are frequently observed in soft tissue sarcomas. To identify genes from this region possibly involved in tumor progression, we analyzed 34 soft tissue sarcomas (10 pleomorphic and 8 dedifferentiated liposarcomas, 6 malignant fibrous histiocytomas, and 10 malignant peripheral nerve sheath tumors (MPNST)) using a DNA microarray including 418 BAC clones representing 99% of chromosome arm 5p. In seven tumors, distinct high-level amplifications were identified affecting four different subregions. From these regions, genes TERT, TRIO, SKP2, FBXO32, NKD2, SLC6A3, IRX2, POLS, FYB, PTGER4, and FGF10 were selected for detailed quantitative expression analysis (RQ-PCR) based on their potential tumorigenic function. Of these, TRIO, coding for a guanidine nucleotide exchange factor, was consistently overexpressed in all cases, while IRX2 and NKD2, both involved in the regulation of developmental processes via the WNT pathway, showed a characteristic expression only in MPNSTs. Detailed nonparametric multidimensional scaling analysis further showed that the expression of TRIO, IRX2, and NKD2 strongly correlated with the gene copy number. In conclusion, we found TRIO, IRX2, and NKD2 frequently affected by high-level amplifications as well as up-regulated in a gene-dosage dependent manner. Thus, these genes represent candidate targets of 5p amplifications in soft tissue sarcomas and might play a crucial role during the progression of this disease.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Soft tissue sarcoma. Epidemiology and prognosis in 508 patients.

We have evaluated epidemiology, prognosis and the association between metastases and local recurrence in a series of adult patients with soft tissue sarcoma (STS) of the extremity and trunk wall. 508 patients were diagnosed in the Southern Swedish Health Care Region from 1964 through 1989. The series was population-based, i.e., all patients within a defined area were included, irrespective of where treated, thereby avoiding selection bias in referral and follow-up. Epidemiology. The annual incidence was 18 per million. The median age was 64 years. One third of the tumors were subcutaneous, and these were smaller than the deep-seated tumors. Malignant fibrous histiocytoma and grade IV were the commonest. Differences were noted in clinicopathologic features among histotypes. The 5-year metastasis-free survival rate (MFSR) was 0.6. The crude local recurrence rate was 0.3. The majority of metastases and local recurrences occurred within 3 years. The referral pattern to the tumor center has become more favorable over time; in the last 5 years half of the subcutaneous and four fifths of the deep-seated tumors were referred before surgery. Prognostic factors. Tumor size, tumor necrosis, and vascular invasion were strong and independent prognostic factors for metastasis in a histologically mixed series. In MFH, storiform and pleomorphic subtype, tumor necrosis and tumor size were associated with a poor prognosis. Tumor necrosis and vascular invasion independently worsened the prognosis in leiomyosarcoma. In liposarcoma, tumor necrosis and in synovial sarcoma, tumor size were the only important prognostic factors. Tumor size, tumor necrosis, and vascular invasion were used in a prognostic system which identified two thirds of all patients with a 5-year MFSR of 0.8 and one third of the patients with a 5-year MFSR of 0.3. Metastasis and local recurrence. The causal association proposed for local recurrence and metastasis should be interpreted with caution. We suggest that highly malignant tumors combine local and distant aggressiveness, and that local recurrence is a marker of risk, and not necessarily a cause of, metastasis. Conclusions. 1. Population-based series are preferable when studying epidemiology in soft tissue sarcoma. 2. We propose that tumor size, tumor necrosis, and vascular invasion are strong and reliable factors that can be used to improve prognostic accuracy. 3. There is a growing body of evidence against a causal relationship between local recurrence and metastasis.

Adolescent↗