Pleomorphic liposarcoma

Abstract

Background Pleomorphic liposarcoma (PLS) is a rare high grade sarcoma showing lipoblastic differentiation. We evaluated PLS natural history, patient outcomes, and commonly deregulated protein biomarkers. Patients and methods PLS patient medical records (n=155; 1993 to 2010) were reviewed. Univariable and multivariable analyses were conducted to identify independent prognosticators. A PLS tissue microarray (TMA; n=56 human specimens) was constructed for immunohistochemical analysis of molecular markers. p53 gene sequencing (exon 5–9) was conducted. Results Average patient age was 57 years with primary (n=102), recurrent (n=16), and metastatic (n=37) presentations. Lower extremity was the most common site (40%); average tumor size was 11cm. Complete follow-up data were available for 83 patients with 22.6 months median follow-up; the 5Y DSS was 53%. Recurrent disease, unresectability, and microscopic positive margins predicted poor prognosis. Systemic relapse (the strongest poor prognostic determinant) occurred in 35% of localized PLS patients. IHC revealed increased expression of PPARγ (adipogenic marker), BCL2 and survivin (survival factors), VEGF (angiogenic factor), MMP2 metalloprotease, and other biomarkers. Frequent loss of Rb expression and high p53 mutation rates (~60%) were identified. Conclusions PLS is an aggressive metastasizing sarcoma. Identifying ubiquitous molecular events underlying PLS progression is crucial for progress in patient management and outcomes.

Extensive Survey of STAT6 Expression in a Large Series of Mesenchymal Tumors

“…Specimens included in the study included whole tumor sections at 4 μm obtained from UMMC and ISMMS (n= 33 and 3 respectively, including 33 solitary fibrous tumors and 3 other sarcomas), sections from a diverse array of previously published sarcoma-specific tissue microarrays, including: soft tissue and uterine leiomyosarcomata, 28, 29 miscellaneous, predominately complex karyotype sarcomas, 30, 31 desmoid tumors, 32, 33 malignant peripheral nerve sheath tumors, 34 angiosarcomas, 35 , alveolar soft part sarcomas, 36 epithelioid sarcoma, 37 myxoid liposarcoma, 38 pleomorphic liposarcoma, 39 well-differentiated/ de-differentiated liposarcoma, 40 and 5 previously unpublished tumor-specific tissue microarrays, including: solitary fibrous tumors (2 arrays, from UTMDACC and ISMMS, respectively, including meningeal hemangiopericytomas), clear cell sarcoma, an additional well-differentiated/de-differentiated liposarcoma array, and neurofibromatosis-associated malignant peripheral nerve sheath tumors.…”

Liposarcoma — spectrum of disease

“…The average age of patients at the time of diagnosis is 53 years (range 14-84 years). Frequent locations of the tumour are thigh soft tissues (34%) and pelvis (15%) [29].…”

“…Like other pleomorphic sarcomas, PLS is characterised by complex chromosomal abnormalities, without a specific molecular marker [29], in particular without amplification of the MDM2 gene, which distinguishes it from DDLPS despite the morphological similarity of these tumours [34].…”

Novel Systemic Therapies in Advanced Liposarcoma: A Review of Recent Clinical Trial Results

“…Disease progression is much more aggressive compared to the other liposarcoma subtypes, with a higher (30–50%) frequency of distant metastasis to visceral organ sites, including lung, bone and liver. Tumors are highly resistant to all current treatment modalities [18,19]. …”