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G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator.

The Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) is a gamma-2 herpesvirus that is implicated in the pathogenesis of Kaposi's sarcoma and of primary effusion B-cell lymphomas (PELs). KSHV infects malignant and progenitor cells of Kaposi's sarcoma and PEL, it encodes putative oncogenes and genes that may cause Kaposi's sarcoma pathogenesis by stimulating angiogenesis. The G-protein-coupled receptor encoded by an open reading frame (ORF 74) of KSHV is expressed in Kaposi's sarcoma lesions and in PEL and stimulates signalling pathways linked to cell proliferation in a constitutive (agonist-independent) way. Here we show that signalling by this KSHV G-protein-coupled receptor leads to cell transformation and tumorigenicity, and induces a switch to an angiogenic phenotype mediated by vascular endothelial growth factor, an angiogenesis and Kaposi's-spindle-cell growth factor. We find that this receptor can activate two protein kinases, JNK/SAPK and p38MAPK, by triggering signalling cascades like those induced by inflammatory cytokines that are angiogenesis activators and mitogens for Kaposi's sarcoma cells and B cells. We conclude that the KSHV G-protein-coupled receptor is a viral oncogene that can exploit cell signalling pathways to induce transformation and angiogenesis in KSHV-mediated oncogenesis.

3T3 Cells↗

The influence of carcinogenic dosage and of sex on the induction of epitheliomas and sarcomas in the dorsal skin of rats.

The effect of varying the numbers (4, 5, 10, 20 and 40) of weekly applications of DMBA to the dorsal skin of intact and castrate male and female rats on the induction of basal and squamous celled epitheliomas and of sarcomas has been investigated.Basal celled tumours originate mainly in hair follicles and squamous celled neoplasms in the interfollicular regions of the epidermis and differ in their progression to malignancy. Penetration of the panniculus carnosus is neither a sufficient nor necessary criterion of malignancy since growing hair follicles pass through the muscle layer and carcinomas and sarcomas which are still confined to the dermis, spread along the perineural lymphatics and metastasise to the lungs.Sex and castration do not affect carcinogenesis of epitheliomas in the dorsal skin at any dose level. Significantly more sarcomas result from 20 weekly paintings in male than in female or castrate rats.The induction period for all tumour types is shortened in sensitive individuals only by an increase from 5 to 10 weekly applications. For less sensitive animals the rate of oncogenesis is accelerated with number of administrations up to 20, but slowed down from this level by 40 paintings. The optimal dose for speed of induction of all tumour types, for maximal yield of basal celled epitheliomas and for that of sarcomas in male rats is 20 weekly applications.THE PROGRESSION TO MALIGNANCY VARIES WITH TUMOUR TYPE: it is fast for sarcomas and slow for basal celled neoplasms. Of the 336 rats at risk only 1% have fibromas or other precursor lesions, while 40% have sarcomas; animals with squamous celled papillomas account for 12%, but those with carcinomas for 66%; there are, however, 64% of rats with basal celled papillomas and only 9% with carcinomas.The optimal dose phenomenon in carcinogenesis is discussed.

Animals↗

Type III collagen metabolism in soft tissue sarcomas.

Sera of 85 patients with benign soft tissue lesions or sarcomas of soft tissues were investigated for a collagen metabolite, the aminoterminal propeptide of type III procollagen (PIIINP). Patients were divided into three groups: benign soft tissue lesions (n = 39), localised (n = 29) and metastatic (n = 18) soft tissue sarcomas (STS). Values of PIIINP above the reference range were found in 15%, 28% and 50% of the respective groups. The difference in the concentration of PIIINP was statistically significant between the benign lesions and the localised sarcomas; P = 0.05, and between the benign lesions and the metastatic sarcomas; P less than 0.001. In localised sarcomas there was a correlation between PIIINP and bone-involvement (r = 0.61, P = 0.002) and in metastatic disease between PIIINP and liver metastases (r = 0.77, P less than 0.001). In localised sarcomas the overall survival for patients with a value of PIIINP above the reference range was significantly poorer (P = 0.03) than for patients with values within the reference range, even after stratification for the histological malignancy grade of the tumours (P = 0.04).

Collagen↗

Efficacy of ifosfamide, dacarbazine, doxorubicin and cisplatin in human sarcoma xenografts.

The primary chemosensitivity of 16 highly malignant xenografted human soft-tissue sarcomas to ifosfamide, dacarbazine, adriamycin and cisplatin and the development of secondary drug resistance in two chemosensitive sarcoma cell lines was tested in the xenograft system. Single-dose, single-agent treatments with 350 mg kg-1 ifosfamide, 200 mg kg-1 dacarbazine, 10 mg kg-1 doxorubicin and 6.6 mg kg-1 cisplatin were administered and response measured as specific growth delay. Since ifosfamide induced unexpectedly higher toxicity, response was corrected based on the shape of the dose-response curve for ifosfamide. Taking a specific growth delay > 3 as the cut-off point for chemosensitivity, ifosfamide, dacarbazine, doxorubicin and cisplatin were effective in 10/16, 4/16, 2/16 and 1/16 sarcoma cell lines respectively. Five out of 16 sarcoma cell lines were resistant to all tested drugs. Ifosfamide-resistant sarcoma lines were also resistant to doxorubicin and cisplatin, indicating a high degree of cross-resistance. Dacarbazine was still effective in 1/6 ifosfamide-resistant sarcoma cell lines. Secondary drug resistance developed slowly after doxorubicin and ifosfamide pretreatments at moderate selection pressure and developed rapidly after dacarbazine pretreatment at high selection pressure.

Animals↗

The association between nm23 gene expression and survival in patients with sarcomas.

The relationship between the expression of nm23, a putative metastasis-suppressor gene and prognosis was determined for 88 patients with sarcomas. Immunohistochemistry using immunopurified anti-nm23 peptide antibodies was performed and the results of each case graded according to the degree of staining. Univariate and multivariate analyses were carried out to determine the prognostic significance of nm23 staining for sarcoma patients. Expression of nm23 was found to increase in line with metastatic potential in many cases but this did not reach significance for the study as a whole. However, the possibility of nm23 loss occurring in association with metastasis cannot be ruled out in some more aggressive sarcomas, as was demonstrated for six patients with low-scoring, unclassified and synovial sarcomas that had metastasized. The time to metastasis was longer for patients with grade 3 sarcomas (50-75% of tumour cells staining) than similar patients in other staining groups. These results suggest that expression of nm23 genes in sarcomas is variable and has no value as a prognostic indicator for these mesenchymal tumours.

Adolescent↗

DNA hypermethylation status of multiple genes in soft tissue sarcomas.

The aberrant methylation of promoter CpG islands is known to be a major inactivation mechanism of tumor-related genes. To determine the clinicopathological significance of gene promoter methylation in soft tissue sarcomas, we examined the promoter methylation status of 10 tumor-related genes in 65 soft tissue sarcomas and 19 adjacent non-neoplastic tissues by methylation-specific PCR. The methylation frequencies of tumor-related genes tested in soft tissue sarcomas were 17 (26%) for RASSF1A, 11 (17%) for DAP kinase, 10 (15%) for MGMT, nine (14%) for GSTP1, eight (12%) for PTEN, six (9%) for p16 and hMLH1, five (8%) for hMSH2, two (3%) for p14, and one (2%) for RB. Promoter methylation of these genes was not recognized in non-neoplastic tissues. All those cases of soft tissue sarcoma that had MGMT methylation, with the exception of one case of malignant peripheral nerve sheath tumor, showed large tumor size (> or = 10 cm) or recurrence. Moreover, eight of 10 cases with MGMT methylation revealed high American Joint Committee on Cancer stage. Seven of 10 cases (70%) with MGMT methylation showed a loss of MGMT expression by immunohistochemistry. In addition, MGMT methylation status had a statistically significant correlation with a loss of MGMT expression (P=0.014). In conclusion, although methylation of tumor-related genes was a relatively rare event in soft tissue sarcomas, methylation was tumor-specific. Of 10 tumor-related genes, cases with MGMT methylation had a tendency to be aggressive behavior. Moreover, MGMT methylation was closely associated with a loss of MGMT expression. Although our findings need to be extending to a large series, promoter methylation of tumor-related genes is likely to have an association with the pathogenesis of soft tissue sarcomas. Furthermore, MGMT methylation may be associated with tumor aggressiveness and the inactivation of MGMT gene.

Adaptor Proteins, Signal Transducing↗

Mutations in the tyrosine kinase domain of the EGFR gene are rare in synovial sarcoma.

The prognosis of patients with synovial sarcomas is poor. New therapeutic strategies, such as target inhibition of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) with erlotinib and gefinitib, could be effective, because most synovial sarcomas overexpress this protein. In lung cancer, the responsiveness to gefinitib is strongly related to the presence of mutations in the tyrosine kinase domain of the EGFR gene, while erlotinib sensitivity seems to be partly linked to chromosome 7 polysomy or gene amplification. To clarify the role of EGFR in synovial sarcoma and to explore the potential for a targeted therapy approach, we have examined 13 of these soft tissue tumors. We have analyzed the EGFR expression by immunohistochemistry, searched for polysomy and gene amplification with fluorescence in situ hybridization (FISH) and screened for EGFR mutations in exons 18-21 using PCR and direct sequencing. All 13 tumors showed strong diffuse or focal EGFR expression. No amplifications of the EGFR gene were found. In contrast, several point mutations were identified in exons 18-21 of two synovial sarcomas. Whereas one of these tumors carried only a synonymous mutation, two missense mutations in exons 19 and 21 of the EGFR gene (P733S and A840 T, respectively) could be demonstrated in the second sample. In conclusion, strong EGFR expression in synovial sarcomas is not related to gene amplification. The existence of mutations in the tyrosine kinase domain of the EGFR gene in a small subset of synovial sarcomas suggests that only few patients may profit from the tyrosine kinase inhibitor therapy.

Adolescent↗

Prognostic significance of apoptosis in synovial sarcoma: correlation with clinicopathologic parameters, cell proliferative activity, and expression of apoptosis-related proteins.

bcl-2 overexpression in synovial sarcomas has been recently reported. Although it is widely known that bcl-2 suppresses apoptosis in various cells, there are no studies that have examined the significance of apoptosis in synovial sarcoma. In the present study, we visualized apoptotic tumor cells by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end-labeling (TUNEL) method in 49 cases of primary synovial sarcoma. The degree of apoptosis was analyzed in relation to several clinicopathologic parameters, cell proliferative activity, and immunohistochemical expression of apoptosis-related proteins, including bcl-2, bax, bcl-x, bak, p53, p21 (WAF1/CIP1), Fas, and Fas ligand. TUNEL index (TUNEL-I) significantly correlated with the mitotic index (MI) (ñ = 0.60, P < .0001) and Ki-67 labeling index (MIB1-I) (ñ = 0.52, P = 0.0005). There was a highly significant association between high TUNEL-I value (>.8%) and poor prognosis (log-rank test; P < .0001). Many synovial sarcomas were diffusely positive for bcl-2 family proteins (bcl-2, bax, bcl-x, and bak) and were negative or only sporadically positive for Fas, Fas ligand, p53, and p21 (WAF1/CIP1) proteins. The results indicated that increased rate of apoptosis in primary synovial sarcoma was considered to be an indicator of poor prognosis. In addition, apoptosis in synovial sarcoma may be controlled by multiple apoptosis-regulating mechanisms, including the bcl-2 family.

Adolescent↗

Orthopaedic implant-related sarcoma: a study of twelve cases.

Sarcoma developing in association with a metallic orthopaedic prosthesis or hardware is an uncommon, but well recognized complication. We review 12 cases of sarcomas arising in bone or soft tissue at the site of orthopaedic hardware or a prosthetic joint. Nine patients were male, and three were female. Their ages ranged from 18 to 85 (mean 55) years at the time of diagnosis of the malignancy. Five patients had undergone hip arthroplasty for degenerative joint disease, four had been treated with intramedullary nail placement for fracture, two had staples placed for fixation of osteotomy, and one had hardware placed for fracture fixation followed years later by a hip arthroplasty. The time interval between the placement of hardware and diagnosis of sarcoma was known in 11 cases and ranged from 2.5 to 33 (mean 11) years. The patients presented with pain, swelling, or loosening of hardware and were found to have a destructive bone or soft tissue mass on radiography. Two sarcomas were located primarily in the soft tissue and 10 in bone. Seven patients developed osteosarcoma, four malignant fibrous histiocytoma, and one a malignant peripheral nerve sheath tumor. All sarcomas were high grade. Three patients had metastatic disease at the time of diagnosis. Follow-up was available on eight patients: five patients died of disease 2 months to 8 years (mean 26 months) after diagnosis; two patients died without evidence of disease 7 and 30 months after diagnosis; and one patient is alive and free of disease 8 years after diagnosis. Sarcomas that occur adjacent to orthopaedic prostheses or hardware are of varied types, but are usually osteosarcoma or malignant fibrous histiocytoma. They behave aggressively and frequently metastasize. Clinically, they should be distinguished from non-neoplastic reactions associated with implants, such as infection and a reaction to prosthetic wear debris.

Adolescent↗

Molecular classification of synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas by gene expression profiling.

In this study, we have used genome-wide expression profiling to categorise synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas (MFHs). Following hierarchical clustering analysis of the expression data, the best match between tumour clusters and conventional diagnosis was observed for synovial sarcomas. Eight of nine synovial sarcomas examined formed a cluster that was characterised by higher expression of a set of 48 genes. In contrast, sarcomas conventionally classified as leiomyosarcomas and MFHs did not match the clusters defined by hierarchical clustering analysis. One major cluster contained a mixture of both leiomyosarcomas and MFHs and was defined by the lower expression of a set of 202 genes. A cluster containing a subgroup of MFHs was also detected. These results may have implications for the classification of soft tissue sarcomas, and are consistent with the view that sarcomas conventionally defined as MFHs do not represent a separate diagnostic category.

Cluster Analysis↗

A link between basic fibroblast growth factor (bFGF) and EWS/FLI-1 in Ewing's sarcoma cells.

The EWS/FLI-1 fusion gene is characteristic of most cases of Ewing's sarcoma and has been shown to be crucial for tumor transformation and cell growth. In this study we demonstrate a drastic down-regulation of the EWS/FLI-1 protein, and a growth arrest, following serum depletion of Ewing's sarcoma cells. This indicates that growth factor circuits may be involved in regulation of the fusion gene product. Of four different growth factors tested, basic fibroblast growth factor (bFGF) was found to be of particular significance. In fact, upon treatment of serum-depleted cells with bFGF, expression of the EWS/FLI-1 protein and growth of the Ewing's sarcoma cells were restored. In addition, a bFGF-neutralizing antibody, which was confirmed to inhibit FGF receptor (FGFR) phosphorylation, caused down-regulation of EWS/FLI-1. Experiments using specific cell cycle blockers (thymidine and colcemide) suggest that EWS/FLI-1 is directly linked to bFGF stimulation, and not indirectly to cell proliferation. We also demonstrated expression of FGFRs in several tumor samples of Ewing's sarcoma. Taken together, our data suggest that expression of FGFR is a common feature of Ewing's sarcoma and, in particular, that the bFGF pathway may be important for the maintenance of a malignant phenotype of Ewing's sarcoma cells through up-regulating the EWS/FLI-1 protein. Oncogene (2000) 19, 4298 - 4301

Adenocarcinoma↗

Cutaneous metastases from Ewing's sarcoma: report of two cases.

Ewing's sarcoma is a malignant osseous neoplasm that affects mostly children and young adult males. Clinically, the neoplasm presents with oedema, swelling, and pain of the involved area. Histopathologically, Ewing's sarcoma consists of solid sheets of small round cells, with vesicular nuclei and scant cytoplasm, arranged in irregular masses separated by strands of fibrous tissue, with areas of necrosis en masse intermingled with intratumoural haemorrhage. Ewing's sarcoma is an extremely aggressive neoplasm and metastases to sites such as lung, pleura, other bones, central nervous system, liver, and regional lymph nodes frequently develop in early stages of the disease. Surprisingly, despite the highly aggressive biological behaviour of this neoplasm, cutaneous metastases from Ewing's sarcoma are very uncommon. We report two patients with Ewing's sarcoma of the bone who developed cutaneous metastases. As in other internal malignancies, the onset of cutaneous metastases in patients with Ewing's sarcoma indicates a poor prognosis.

Adult↗

Differential Ki67 and bcl-2 immunoexpression in solid-glandular and spindle cell components of biphasic synovial sarcoma: a double immunostaining assessment with cytokeratin and vimentin.

AIMS: Synovial sarcoma is a malignant soft tissue of uncertain histogenesis that may show a biphasic (spindle and solid/glandular components) or a monophasic histological appearance. In previous studies, we demonstrated that the solid/glandular component possesses higher proliferation rates than the spindle cell component of biphasic synovial sarcomas and that the spindle cell component may exhibit a progressive transition from or to the solid-glandular component in biphasic synovial sarcoma. To evaluate this hypothesis further, we designed a novel approach to correlate immunoexpression of Ki67, bcl-2 and bax in the spindle cell and in the solid-glandular component of biphasic synovial sarcomas. We also performed a double-immunohistochemical assessment of the Ki67 proliferative indices and the immunoexpression of anti-apoptotic protein bcl-2 in neoplastic cells expressing either vimentin or cytokeratin. METHODS AND RESULTS: Immunohistochemistry for vimentin (10 cases), bcl-2 (10 cases), Ki67(10 cases), cytokeratin (10 cases), and bax (eight cases), and double-immunostaining for vimentin/Ki67 (10 cases), vimentin/bcl-2 (nine cases), cytokeratin/Ki67 (10 cases), and cytokeratin/bcl-2 (10 cases) assays were performed in 10 cases of primary biphasic synovial sarcoma. Semiquantitative assessment was adopted for each case in both components. Statistical analysis was performed using Fisher's exact test or chi2 test. On conventional immunohistochemistry, the solid/glandular component revealed more expression of Ki67, bax and cytokeratin than the spindle cell component (P=0.0004, P=0.082, and P < 0.0001, respectively); on the other hand, the latter showed higher expression of bcl-2 and vimentin than the former (P=0.0281 and P=0.059, respectively). Double immunohistochemistry analysis revealed higher co-expression levels of cytokeratin/Ki67 and cytokeratin/bcl-2 than the spindle cell component (P=0.015 and P < 0.0001, respectively); conversely, the latter presented higher co-expression of vimentin/bcl-2 than the former (P=0.0007). All cases showed no more than 10% of cells coexpressing cytokeratin/bcl-2, cytokeratin/Ki67, and no case revealed cells coexpressing vimentin/Ki67. CONCLUSION: Our findings indicate that in biphasic synovial sarcoma the acquisition of epithelial phenotype (solid/glandular component) is associated with a high expression of pro-apoptotic proteins and a high proliferative differentiation status, and conversely, mesenchymal phenotype (spindle cell component) is associated with a high expression of apoptosis-inhibitor bcl-2 and a low proliferative terminal-type differentiation status.

Adult↗

Uterine sarcoma: can it be differentiated from uterine leiomyoma with Doppler ultrasonography? A preliminary report.

Our objective was to evaluate whether intratumoral-blood flow analysis could differentiate uterine sarcoma from uterine leiomyoma. Color and pulsed Doppler findings obtained from 41 patients with histologically proven uterine leiomyoma and five with uterine sarcoma (four leiomyosarcoma, one mixed mesodermal tumor) were retrospectively assessed. Intratumoral blood flow velocity waveforms were recorded, and the resistance index (RI) and peak systolic velocity (PSV) were calculated. There was no significant difference between the RI (median 0.647; range 0.422-0.896) in the uterine leiomyomas and the RI (median 0.663; range 0.330-0.774) in the uterine sarcomas. The PSV (median 61.6 cm/s; range 40.0-124.0 cm/s) in the uterine sarcomas was significantly higher (median 21.6 cm/s, range 6.3-48.6 cm/s) than that in the uterine leiomyomas (p < 0.05). When a cut-off value for the PSV of 41.0 cm/s (mean PSV of the uterine leiomyomas plus 2 standard deviations) was considered, the detection rate for uterine sarcoma was 80.0%, and the false-positive rate was 2.4%. These results suggest that the PSV within the tumor detected by color and pulsed Doppler ultrasonography could be useful for the preoperative differential diagnosis of uterine sarcoma.

Adult↗

Microsatellite instability in uterine sarcomas.

Studies have shown a 15-30% frequency of microsatellite instability in endometrial cancer. In addition, we found a 21% frequency of microsatellite instability in endometrial cancer. Our aim was to investigate the presence of microsatellite instability and loss of heterozygosity in uterine sarcomas. The records of 69 women referred to Kalafong Academic and Pretoria Academic Hospital with a primary diagnosis of uterine sarcoma were reviewed. At histological review of 43 cases with a primary diagnosis of leiomyosarcoma, diagnosis of mitotically active leiomyoma was made in 21. Diagnosis of carcinosarcoma was made in 21 cases and endometrial stromal sarcoma in five. In all cases, genomic DNA was extracted from normal myometrium and tumor and analyzed for microsatellite instability and loss of heterozygosity. High-frequency microsatellite instability was absent in leiomyosarcoma, endometrial stromal sarcoma, and mitotically active leiomyomas and was observed in 1 (5%) carcinosarcoma. Loss of heterozygosity for chromosome 11 was present in 8/48 (17%) of uterine sarcomas, equally distributed between leiomyosarcomas (4/22 = 18%) and carcinosarcomas (4/21 = 19%). There was no loss of alleles in endometrial stromal sarcoma nor mitotically active leiomyomas. In conclusion, it is suggested that tumor suppressor genes may play a role in the tumorigenesis of uterine mesenchymal cells, whereas mismatch repair genes contribute to the carcinogenesis of endometrial cancer.

Carcinosarcoma↗

Sarcoma of the oral and maxillofacial soft tissue in adults.

AIMS: Sarcoma occurring in oral and maxillofacial soft tissue is rare. This study was carried out to evaluate the prevalence of oral soft tissue sarcoma and to record its natural history and survival. METHODS: Retrospective analysis of the patients with histologically proven oral and maxillofacial soft tissue sarcoma treated at the Regional Cancer Centre (RCC), Trivandrum, betweeen 1990-1998 was carried out. RESULTS: During this period, ten cases of oral and maxillofacial sarcomas were registered. Three lesions were located on the cheek mucosa, two on the tongue and two on the mandibular alveolus, while there was one lesion each in the parotid region, maxilla and face (NOS). Mean age at presentation was 31.3+/-14.1 years (range 15-54 years). Seven of the patients (70%) were males. There were three cases of rhabdomyosarcoma (RMS), three cases of spindle cell sarcoma and one case each of angiosarcoma, haemangioendothelioma, malignant schwannoma and malignant fibrous histiocytoma (MFH). All the patients were treated with surgery as a primary modality. Median follow-up time was 30 months (range 5-94 months). An overall srvival of 87.5% at 5 years was observed; however, 5-year disease free survival was 60.0% (95% CI 19.5-85.2). CONCLUSIONS: Soft tissue sarcomas are of comparatively less frequent occurrence in oral and maxillofacial soft tissue than in other tissues. A good survival rate can be achieved by multimodality treatment.

Adolescent↗

Upper-extremity sarcomas in the United States: analysis of the surveillance, epidemiology, and end results database, 1973-1998.

PURPOSE: Upper-extremity soft-tissue sarcomas are a rare disease with unclear epidemiology and evolving treatment strategies. Our purpose is to evaluate the incidence of upper-extremity soft-tissue sarcomas and the use of adjuvant radiotherapy in this patient population. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, a national population-based database, we identified all cases of primary upper-extremity sarcoma reported to the 9 national SEER registries in the Untied States from 1973 to 1998. RESULTS: Of the 1,286 upper-extremity soft-tissue sarcomas the average incidence rate is 2.2 cases/million/y, which has not changed significantly from 1973 to 1998. Caucasians' average incidence rate is significantly higher than African Americans' (incidence rate ratio [IRR] = 1.3, p =.02); and men are at a significantly higher risk compared with women (IRR = 1.3, p <.01). The use of adjuvant radiotherapy has increased significantly from 17% in 1973 to 47% in 1998 (p <.01). African-Americans, compared with Caucasians, are significantly less likely to receive adjuvant radiotherapy (odds ratio [OR] =.5, p =.01). CONCLUSIONS: The incidence of upper-extremity sarcomas has not changed significantly over the past 3 decades; however, the disease differentially affects the population with higher rates in Caucasians and men. Based on the results of this study the use of adjuvant radiotherapy is increasing but African Americans are less likely than Caucasians to receive this treatment for upper-extremity sarcoma.

Black or African American↗

Concentration of vascular endothelial growth factor in the tumour tissue as a prognostic factor of soft tissue sarcomas.

Previous studies have shown that the prognosis of patients who have tumours with high microvessel density (MVD) is worse than that of patients who have a lower density in a variety of cancers. In this study, we investigated the clinical relevance of neovascularity assessed by MVD and the concentration of vascular endothelial growth factor (VEGF) in the tumour tissue of patients with soft tissue sarcoma in comparison with major clinicohistologic parameters by univariate and multivariate analysis. In 115 patients with soft tissue sarcoma, MVD was measured by counting vessels stained with factor VIII antibody. The concentration of VEGF in the tumour tissue was determined by enzyme-linked immunosorbent assay. These parameters were then compared with disease outcome. The concentration of VEGF in the tumour tissue, but not MVD, was found to be correlated with disease outcome in patients with soft tissue, sarcoma. VEGF concentration in the tumour tissue showed a relationship with the clinical stage and histologic grade of the tumour. There was no significant difference in the levels of tissue VEGF concentration and MVD among soft tissue sarcomas classified according to histologic type. The level of tissue VEGF concentration in patients who had subsequent local recurrence and metastasis were significantly higher than the respective values in patients who did not have such disease outcome. No significant correlation existed between MVD and the concentration of VEGF in the tumour tissue. Univariate analysis showed that a high tissue VEGF concentration was associated with poor overall survival of the patient and a greater probability that local recurrence and metastasis had occurred. Multivariate analysis revealed that the tissue concentration of VEGF is an independent prognostic factor for the disease outcome of patients with soft tissue sarcoma. VEGF concentration in the tumour tissue, but not MVD, is an additional prognostic parameter for disease outcome in patients with soft tissue sarcoma, regardless of histologic type.

Adult↗