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Superficial soft tissue sarcomas (sSTS) are an important and frequent subtype of soft tissue sarcoma (STS). A wider knowledge of this tumor type may lead to better strategies in tumor therapy. An institutional review was performed on all patients with primary sSTS of the extremities and trunk operated on between 1990 and 2003. The medical records of 108 patients with sSTS were analyzed. The local recurrence rate was 11% after a median of 25 (mean 42) months. Metastases occurred in 21 patients (19%), and 79 patients lived without evidence of disease after a mean follow-up of 112 ± 42 months. Mean survival time was 89 months at a cumulative 5-year survival rate of 85%. R0 resection significantly enhanced cumulative survival ( p = .001), as did patient age < 60 years ( p = .002), tumor grading G1 and G2 compared to G3 ( p = .004), absence of positive lymph nodes ( p = .018), and no occurrence of metastases ( p = .001). Tumor size ≤ 5 cm reduced the local recurrence rate significantly ( p = .044). Significant multivariate risk factors for metastases were age ≥ 60 years ( p = .016) and tumor grade G3 ( p = .021). Patients with sSTS who are ≥60 years of age or who have G3 tumors have a high risk of distant metastases. Patients with T2 tumors have an elevated risk for local recurrence. Certainly all patients with sSTS should be in a tight after-care program to allow early diagnosis of local recurrence or distant metastases. Age < 60 years, tumor grade G1/2, no positive regional lymph nodes (N0), and a R0 resection are significant prognostic factors for survival. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the relationship between chromosomal instabilities and clinicopathological factors in synovial sarcoma (SS). Methods: Twenty-two fresh-frozen SS were analyzed by metaphase comparative genomic hybridization (CGH). Additional microarray CGH was performed in 13 cases. Results: Fourteen patients with SYT–SSX1 rearrangements and nine patients with biphasic tumor subtypes had better prognosis than the eight patients with SYT–SSX2 rearrangements and 13 patients with monophasic subtypes, respectively. Gains (average 3.0) were more frequent than losses (average 1.0). Frequent gains were identified on chromosomal regions 2, 6q, 7, 8q, 12, 17q, 18q, and 21q, whereas frequent losses were over-lapped on chromosomes 1p31–p35, 3p, 6q, 16, and 17p. High-level gains were observed on chromosomes 1q21–q31, 7, 8, 12, 17q, 18q, and 21q. Thirteen monophasic and nine biphasic tumors had an average of 5.1 and 2.8 aberrations, respectively. Patients with tumors harboring numerous aberrations (≥3) had a worse clinical course. Microarray CGH more specifically detected genetic imbalances including gains in MDM2, MSH2, KCNK12, DCC, CDK2, ERBB3, SAS, and CDK4 and losses in HRAS, RASSF1, and CCND1. Gain of SAS was an important prognostic factor of SS. Conclusion: We have identified several factors influencing the prognosis of SS patients by metaphase and microarray CGH. [ABSTRACT FROM AUTHOR]

Abstract: In Ewing’s sarcoma family of tumours (ESFT), the clinically most adverse prognostic parameters are the presence of tumour metastasis at time of diagnosis and poor response to neoadjuvant chemotherapy. To identify genes differentially regulated between metastatic and localised tumours, we analysed 27 ESFT specimens using Affymetrix microarrays. Functional annotation of differentially regulated genes revealed 29 over-represented pathways including PDGF, TP53, NOTCH, and WNT1-signalling. Regression of primary tumours (n =20) induced by polychemotherapy was found to be correlated with the expression of genes involved in angiogenesis, apoptosis, ubiquitin proteasome pathway, and PI3 kinase and p53 pathways. These findings could be confirmed by in vitro cytotoxicity assays. A set of 46 marker genes correctly classifies these 20 tumours as responding versus non-responding. We conclude that expression signatures of initial tumour biopsies can help to identify ESFT patients at high risk to develop tumour metastasis or to suffer from a therapy refractory cancer. [Copyright &y& Elsevier]

Clear cell sarcoma of soft tissue (CCSST) represents a highly malignant tumor of the musculoskeletal system that is characterized by the chromosomal translocation t(12;22)(q13;q12) of the Ewing sarcoma gene (EWSR1) and activating transcription factor 1 (ATF1). In a former microarray expression study, we identified ERBB3, a member of the epidermal growth factor receptor (EGFR) family, as a promising new diagnostic marker in the differential diagnosis of CCSST. Here we show that, besides ErbB3, all CCSST cell lines (n = 8) also express the ErbB2 receptor or the ErbB4 receptor, representing an adequate coreceptor of ErbB3. The phosphorylation status of ErbB3 revealed these receptor pairs to be either constitutively activated in CCSST cells with high neuregulin-1 (NRG1) expression (n = 4) or activatable by exogenic NRG1 in cells showing low amounts of NRG1 mRNA (n = 4). Exogenous NRG1 stimulated the growth of a subset of CCSST cells but did not affect the kinetics of another subset. This difference was not strictly dependent on endogenous NRG1 expression; however, the growth-inhibiting effect of the pan-ErbB tyrosine kinase inhibitor CI-1033 or PD158780 clearly correlated with NRG1 expression indicating an autocrine growth stimulation loop, which may constitute an interesting target of new therapeutic strategies in this tumor entity. [ABSTRACT FROM AUTHOR]