Change in histological grade in locally recurrent soft tissue sarcomas

Histological examination of locally recurrent soft tissue sarcomas usually reveals an appearance similar to that of the original tumour. Occasionally, however, recurrent sarcomas appear more or less malignant histologically than the initial lesion. The goals of this paper were to identify the frequency with which this phenomenon occurs, factors that predict for a change in grade and to determine if this change is associated with a different prognosis from other patients with local recurrence. From a large sarcoma database, 124 patients with local recurrence were identified. These patients were distributed into groups who had no change in histological grade, increased histological grade or decreased histological grade on local recurrence. Increased grade occurred approximately 20% of the time, whereas decreased grade occurred in 7% of cases. A histological diagnosis of myxofibrosarcoma was predictive of an increase in histological grade on local recurrence. An increase in histological grade with local recurrence was not associated with a poorer survival.     

Metalloproteinase expression and prognosis in soft tissue sarcomas

Background:Degradation of extracellular matrix bytumor-associated proteases can promote cell invasion and metastasis. Thisstudy assessed the prognostic role of MMP2, MMP9 metalloproteinases, and ofthe metalloproteinase inhibitor TIMP2, related to disease-free survival (DFS),in soft tissue sarcoma (STS) patients. Materials and methods:Level and distribution of MMP2, MMP9, andTIMP2 expression were evaluated on 73 biopsies by immunohistochemistry andimmunoblotting. Biopsies included 29 liposarcomas, 29 synovial sarcomas, and15 malignant peripheral nerve sheath tumors (MPNST).Association between DFS and overall survival with different variables wasassessed. Results:In terms of DFS, increased MMP2 reactivity and lack ofTIMP2 expression were significant for poor prognosis in all samples(P = 0.0005 and P = 0.006 respectively). MMP2correlated to histologic grade (P = 0.005). Lack of TIMP2expression was a poor prognostic factor for DFS in synovial sarcoma(P = 0.009), while MMP2 and MMP9 correlated with metastasis(P = 0.008 and P = 0.005, respectively) and grade(P = 0.001 and P = 0.04 respectively) inliposarcoma. Conclusions:These prognostic markers that influence growth andspread of tumor cells might be useful to define tumor aggressiveness and riskof the metastasic event.     

Radiation therapy for high grade soft tissue sarcomas of the extremities treated with limb-preserving surgery.

AIM: It is common to use either pre- or post-operative radiation for high grade sarcomas undergoing limb-conserving surgery. Since 1977, we have adopted a selective policy of post-operative radiation, given only in patients with inadequate surgical margins. METHODS: A retrospective review of 114 patients (1977-1995) with high grade adult soft tissue sarcomas of the extremities was carried out. Amputation was required in 10 (9%). Patients with a minimum surgical margin <2 cm (n=33) received adjuvant radiation (29%). RESULTS: No complications occurred in 81/114. Wound complications were infection (14%), seroma (6%), haematoma (4%), dehiscence (4%) and skin edge necrosis (2%). Remedial operations were required in four (3%). Overall, the local recurrence rate was 23/114. Patients with surgery only (n=57) or surgery plus systemic chemotherapy (n=24) manifested local recurrence in 15/81 (19%) and those with surgery plus radiation (n=21) or surgery and radiation and chemotherapy (n=12) suffered local recurrence in 8/33. The local recurrence rate for tumours < or =5 cm was 6/32 and for those >5 cm 17/82, P=1.0. The 5 year survival rate was 60% for tumours < or =5 cm (n=32) and 46% for tumours > or =5 cm (n=82) (P=0.009). CONCLUSIONS: (1) Limb preservation was feasible in 91% of patients. (2) When the local treatment modality was surgery alone ('wide' margins) the local recurrence rate was 19%, and when it was surgery plus radiation (narrow margins) it was 24%. (3) Selective use of radiation (in patients with narrow margins) and reliance on surgery alone in cases amenable to wide resection may be a legitimate alternative to universal application of radiation with conservative resection.     

Skp2 protein expression in soft tissue sarcomas.

BACKGROUND: p45 S phase kinase-associated protein-2 (p45(skp2)), a member of the F-box family of proteins, is an important component of the Skp1-Cullin-F-box protein (SCF) ubiquitin-ligase complex (SCF(skp2)). The latter has been implicated in the ubiquitination and degradation of p27(kip1) (p27) and G(1)-S cell cycle progression. The expression and prognostic role of Skp2 in a large series of soft tissue sarcomas has not been previously investigated. METHODS: Clinicopathologic features and immunohistochemical expression of Skp2, p27, and Ki-67 proteins were studied in 182 cases of soft tissue sarcomas (American Joint Committee on Cancer stages II and III). Survival analyses were performed using the Kaplan-Meier method and the Cox regression model. RESULTS: The male to female ratio was 1.2:1, and the median age at the diagnosis was 53 years. The tumors were predominantly located in the lower extremities (n = 163; 90%) and had a median size of 9 cm. High Skp2 expression (> or = 10% of the cells) was identified in 68 tumors (37%), and was correlated with high grade histology (P =.002) and Ki-67 proliferative index (r = 0.44; P <.0001), but not with p27 expression (r = -0.02; P =.80). By univariate analysis, high Skp2 expression was associated with decreased metastasis-free, disease-free, and overall survival. In a multivariate model, high Skp2 expression was an independent predictor for decreased local recurrence-free, disease-free, and overall survival. CONCLUSION: These results indicate that Skp2 expression is associated with cell proliferation and a worse prognosis in soft tissue sarcomas. The lack of an inverse correlation between Skp2 and p27 suggests that additional molecular events associated with either Skp2 expression or p27 proteolysis may be operating in these tumors.     

High incidence of metastatic disease in primary high grade and large extremity soft tissue sarcomas treated without chemotherapy

Background  

The risk of metastasis and the survival in patients with primary extremity soft tissue sarcomas is worse when tumour size is large and the grade of malignancy is high. Such tumours may receive chemotherapy and/or radiation therapy (RTX) for optimising local control. Irradiation can either be applied preoperatively or after tumour resection. The question arises if the kind of RTX in the absence of chemotherapy influences the outcome concerning local control, metastatic disease, survival and complications.     

Follow-up in soft tissue sarcomas

The strategy for the follow-up of soft tissue sarcomas (STS) after therapy is tailored to the individual risk of recurrence and based on efficient rather than sophisticated methods of observation. Along with advances in the treatment of sarcomas, earlier detection of a less advanced and resectable recurrent disease (local or metastasis—especially to the lungs) can prolong patient survival. Since the majority of STS relapses occur within 5 years after treatment (approximately 80?% of metastases to the lung and close to 70?% of local recurrences within the first 2–3 years), in the period between 2 and 3 years after treatment, it is mandatory to follow-up patients every 3 months and perform careful history and physical examination (especially scars after surgery of the primary site) and a chest X-ray. There is no reason to perform other studies in asymptomatic patients (unless the patient reports symptoms). In case of retroperitoneal or intraperitoneal STS (including gastrointestinal stromal tumor), contrast-enhanced computed tomography of the abdomen and pelvis is recommended as the follow-up modality of choice. In this paper we outline the current recommendations for the follow-up strategy.     

Pediatric soft tissue sarcomas

Many of the soft tissue sarcomas that occur in children are of the same histology as those in adults; however, the relative prevalence of these sarcomas is different between children and adults. In some cases, the biologic behavior of pediatric sarcomas is more benign than that in adults. Treatment for sarcomas in children is also different. Pediatric sarcomas are more commonly responsive to chemotherapy. Furthermore, in children who are still growing, surgery and radiation are associated with higher morbidity than in adults. This article discusses the diagnosis and treatment of rhabdomyosarcoma and undifferentiated sarcomas, with an emphasis on surgical considerations, and the diagnosis and treatment of nonrhabdomyosarcomatous soft tissue sarcomas in children.     

Pelvic soft tissue sarcomas

Pelvic soft tissue sarcomas (PSTS) are a rare, heterogeneous group of tumors. They have been usually analyzed with retroperitoneal sarcomas (RPS), but actually have key differences. Due to their unique anatomic location, symptomatic presentation of PSTS may be more common than RPS. Adequate imaging approach is paramount for guiding differential diagnosis, while preoperative biopsy is mandatory, especially when preoperative treatment may be considered as initial approach. The most frequent histologic subtype is leiomyosarcoma, which is different as expected in the retroperitoneum where liposarcoma is the commonest histology. Also solitary fibrous tumor is commonly diagnosed in the pelvis. Surgical approach for PSTS differs from that for RPS mainly due to anatomic relations. Similarly, in the lack of definite evidence from specific trials about neoadjuvant and adjuvant treatments, the anatomic constraints to obtain wide margins in the pelvis as well as the expected functional outcome in case of organ resections should be factored into decision for individualized treatment offer. Vascular and genitourinary involvement are frequent, as well as herniation through pelvic foramina. For these reasons a multidisciplinary surgical team should always be considered. Early referral of these patients to high-volume centers is critical and may impact on survival, given that optimal initial resection is a major predictor of curative treatment. International consensus on PSTS treatment is advocated, similarly to the recent efforts realized for RPS.     

Immunohistochemical expression of promyelocytic leukemia body in soft tissue sarcomas

Background

The function of promyelocytic leukemia (PML) bodies is not well known but plays an important role in controlling cell proliferation, apoptosis and senescence. This study was undertaken to analyze the clinical significance of PML body expression in primary tumor samples from malignant fibrous histiocytoma (MFH) and liposarcoma patients.

Methods

We studied MFH and liposarcoma samples from 55 patients for PML bodies. Fluorescent immunostaining of PML bodies was performed in the paraffin-embedded tumor sections.

Results

PML body immunostaining was identified in 63.9% of MFH and 63.2% of liposarcoma samples. PML body expression rates of all sarcoma cells were 1.5 ± 1.8% (range: 0–7.0) in MFH and 1.3 ± 1.4% (0–5.2) in liposarcoma samples. PML body expression (p = 0.0053) and a high rate of PML body expression (p = 0.0012) were significantly greater prognostic risk factors for death than the other clinical factors in MFH patients. All liposarcoma patients without expression of PML were disease free at the end of the study.

Conclusion

Our study suggests that the presence of PML bodies may indicate a poor prognosis for MFH and liposarcoma patients.     

Apoptosis and expression of its regulatory proteins in soft tissue sarcomas

Information for the occurrence and extent of apoptosis in soft tissue sarcoma (STS) and their clinical implication are limited. In 102 cases of STSs, apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method and expression of Bcl-2, Bax, MIB-1 and p53 protein was examined immunohistochemically. The apoptotic index of the STSs ranged from 0 to 15% with an average value of 1.9%. The mean values of positive cell staining for Bcl-2, Bax, MIB-1 and p53 protein were 32.1, 40.8, 17.0 and 20.3%, respectively. The extent of apoptosis and expression of Bcl-2 protein were correlated to the histologic types of the tumor. Synovial sarcoma had a significantly higher expression of Bcl-2 protein, and lower incidence of apoptosis. STS underwent apoptosis at a constitutional level. There were no significant relationships between extent of the apoptosis, expression of its regulatory proteins and prognosis of the patients.     

Chemotherapy in soft tissue sarcomas]

Despite they represent an heterogeneous entity, the same protocols were applied to all subtypes of soft-tissue sarcomas until recently. Although doxorubicin and ifosfamide remain the cornerstone of therapy, their association yields enhanced response rates but has no obvious effect on survival. The benefit of adjuvant therapy is still matter of debate; however, it seems to improve relapse-free survival and might of particular interest for patients with high-grade tumours of the extremities. Yet, the major change occurring over the past few years is probably the development of subtype-specific regimens. Whether targeted therapies could provide additional benefit is a major concern but further studies are needed.     

Multiple primary soft tissue sarcomas

BACKGROUND: The synchronous or metachronous development of multiple primary soft tissue sarcomas (STS) of different histopathology has been reported only in isolated case reports. METHODS: The records of patients who developed multiple primary STS and who were treated at a tertiary cancer center between 1982 and 2003 were reviewed. RESULTS: Nine patients with multiple primary STS were identified, representing 0.2% of all patients who were treated for STS. The median age of patients at the time of initial presentation with sarcoma was 60 years (range, 51-81 years). Most patients in this series (n = 7) had metachronous development of a second primary STS. The incidence of second primary sarcomas in patients who were diagnosed previously with STS (4.0 per 10,000 population per year) was significantly greater than the incidence of primary STS in the general population (3.2 per 100,000 population per year; P < 0.01). CONCLUSIONS: Although it is an uncommon occurrence, patients who have a history of STS are at an increased risk for the development of a second primary STS.     

Brachytherapy in soft tissue sarcomas]

Soft tissue sarcomas are rare tumors with a high risk or local recurrence and a risk of distant metastases. Standard treatment advocated is the combination of conservative resection and external radiotherapy. Brachytherapy is an integrated part of the multidisciplinary treatment. Brachytherapy can increase local control with good functional results. Primary exclusive brachytherapy has been used and is effective and safe in high grade sarcomas (randomized trial of MSKCC). Brachytherapy seems to be important as part of the treatment of central localization (shoulder, groin) and sarcomas with positive resection margins, but its relation with external radiotherapy has to be defined. Brachytherapy used with special guidelines allows to obtain an improved local control with an acceptable level of complication.     

Update on soft tissue sarcomas

Important refinements have taken place in the diagnosis of soft tissue sarcoma with extensive use of immuno-histochemistry. New entities have been described, while malignant histiocytofibroma, the most diagnosed sarcoma type during the last two decades, has been dismembered. As for prognosis, the new UICC classification is effectively more discriminating in the definition of prognostic groups; but the usefullness of new biological or genetic markers remains to be assessed. Several breakthrough have taken place in the last years in the treatment of soft tissue sarcoma. Isolated limb perfusion with TNF, hyperthermia and melphalan have proven its efficacy, and is now an alternative to preoperative chemotherapy and/or radiotherapy for limb sparing treatment of the primary tumor site or to amputation. For systemic treatments, novel cytostatic drugs have been shown to be active in sarcomas, including ecteinascidine (ET743) and Glivec (STI571). This last drug has been shown to be remarkably active in c-kit+ stromal sarcoma of the gastro-intestinal tract. It can hopefully regarded as an example for targeted therapies, which may come with a better understanding of the molecular mechanisms triggered by the fundamental, specific genetic alterations shown in sarcoma.