Pleomorphic liposarcoma

Clinical observations and molecular variables

Markus P. Ghadimi, Ping Liu, Tingsheng Peng, Svetlana Bolshakov, Eric D. Young, Keila E. Torres, Chiara Colombo, Aviad Hoffman, Dominique Broccoli, Jason L. Hornick, Alexander J. Lazar, Peter Pisters, Raphael E. Pollock, Dina Lev

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Pleomorphic liposarcoma (PLS) is a rare high-grade sarcoma that has lipoblastic differentiation. In this study, the authors evaluated PLS natural history, patient outcomes, and commonly deregulated protein biomarkers. METHODS: Medical records from patients (n = 155) who had PLS from 1993 to 2010 were reviewed. Univariate and multivariate analyses were conducted to identify independent prognosticators. A PLS tissue microarray (TMA) (n = 56 patient specimens) was constructed for immunohistochemical analysis of molecular markers, and p53 gene sequencing (exons 5-9) was conducted. RESULTS: The average patient age was 57 years, and the patients presented with primary disease (n = 102), recurrent disease (n = 16), and metastatic disease (n = 37). Lower extremity was the most common disease site (40%), and the average tumor size was 11 cm. Complete follow-up data were available for 83 patients, and their median follow-up was 22.6 months. The 5-year disease-specific survival rate was 53%; and recurrent disease, unresectability, and microscopic positive margins were identified as predictors of a poor prognosis. Systemic relapse (the strongest poor prognostic determinant) developed in 35% of patients with localized PLS. Immunohistochemical analysis revealed increased expression of peroxisome proliferator-activated receptor gamma (an adipogenic marker), B-cell leukemia 2 and survivin (survival factors), vascular endothelial growth factor (an angiogenic factor), matrix metalloproteinase 2, and other biomarkers. Frequent loss of retinoblastoma protein expression and high p53 mutation rates (approximately 60%) were observed. CONCLUSIONS: PLS is an aggressive, metastasizing sarcoma. Identifying ubiquitous molecular events underlying PLS progression is crucial for progress in patient management and outcomes.

Original languageEnglish
Pages (from-to)5359-5369
Number of pages11
JournalCancer
Volume117
Issue number23
DOIs
Publication statusPublished - Dec 1 2011

Fingerprint

Liposarcoma
Sarcoma
Biomarkers
B-Cell Leukemia
Retinoblastoma Protein
Angiogenesis Inducing Agents
PPAR gamma
Matrix Metalloproteinase 2
p53 Genes
Mutation Rate
Natural History
Vascular Endothelial Growth Factor A
Medical Records
Lower Extremity
Exons
Multivariate Analysis
Survival Rate
Recurrence
Survival

Keywords

  • clinical outcome
  • molecular biomarkers
  • p53 mutations
  • pleomorphic liposarcoma
  • tissue microarray

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ghadimi, M. P., Liu, P., Peng, T., Bolshakov, S., Young, E. D., Torres, K. E., ... Lev, D. (2011). Pleomorphic liposarcoma: Clinical observations and molecular variables. Cancer, 117(23), 5359-5369. https://doi.org/10.1002/cncr.26195

Pleomorphic liposarcoma : Clinical observations and molecular variables. / Ghadimi, Markus P.; Liu, Ping; Peng, Tingsheng; Bolshakov, Svetlana; Young, Eric D.; Torres, Keila E.; Colombo, Chiara; Hoffman, Aviad; Broccoli, Dominique; Hornick, Jason L.; Lazar, Alexander J.; Pisters, Peter; Pollock, Raphael E.; Lev, Dina.

In: Cancer, Vol. 117, No. 23, 01.12.2011, p. 5359-5369.

Research output: Contribution to journalArticle

Ghadimi, MP, Liu, P, Peng, T, Bolshakov, S, Young, ED, Torres, KE, Colombo, C, Hoffman, A, Broccoli, D, Hornick, JL, Lazar, AJ, Pisters, P, Pollock, RE & Lev, D 2011, 'Pleomorphic liposarcoma: Clinical observations and molecular variables', Cancer, vol. 117, no. 23, pp. 5359-5369. https://doi.org/10.1002/cncr.26195
Ghadimi MP, Liu P, Peng T, Bolshakov S, Young ED, Torres KE et al. Pleomorphic liposarcoma: Clinical observations and molecular variables. Cancer. 2011 Dec 1;117(23):5359-5369. https://doi.org/10.1002/cncr.26195
Ghadimi, Markus P. ; Liu, Ping ; Peng, Tingsheng ; Bolshakov, Svetlana ; Young, Eric D. ; Torres, Keila E. ; Colombo, Chiara ; Hoffman, Aviad ; Broccoli, Dominique ; Hornick, Jason L. ; Lazar, Alexander J. ; Pisters, Peter ; Pollock, Raphael E. ; Lev, Dina. / Pleomorphic liposarcoma : Clinical observations and molecular variables. In: Cancer. 2011 ; Vol. 117, No. 23. pp. 5359-5369.
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abstract = "BACKGROUND: Pleomorphic liposarcoma (PLS) is a rare high-grade sarcoma that has lipoblastic differentiation. In this study, the authors evaluated PLS natural history, patient outcomes, and commonly deregulated protein biomarkers. METHODS: Medical records from patients (n = 155) who had PLS from 1993 to 2010 were reviewed. Univariate and multivariate analyses were conducted to identify independent prognosticators. A PLS tissue microarray (TMA) (n = 56 patient specimens) was constructed for immunohistochemical analysis of molecular markers, and p53 gene sequencing (exons 5-9) was conducted. RESULTS: The average patient age was 57 years, and the patients presented with primary disease (n = 102), recurrent disease (n = 16), and metastatic disease (n = 37). Lower extremity was the most common disease site (40{\%}), and the average tumor size was 11 cm. Complete follow-up data were available for 83 patients, and their median follow-up was 22.6 months. The 5-year disease-specific survival rate was 53{\%}; and recurrent disease, unresectability, and microscopic positive margins were identified as predictors of a poor prognosis. Systemic relapse (the strongest poor prognostic determinant) developed in 35{\%} of patients with localized PLS. Immunohistochemical analysis revealed increased expression of peroxisome proliferator-activated receptor gamma (an adipogenic marker), B-cell leukemia 2 and survivin (survival factors), vascular endothelial growth factor (an angiogenic factor), matrix metalloproteinase 2, and other biomarkers. Frequent loss of retinoblastoma protein expression and high p53 mutation rates (approximately 60{\%}) were observed. CONCLUSIONS: PLS is an aggressive, metastasizing sarcoma. Identifying ubiquitous molecular events underlying PLS progression is crucial for progress in patient management and outcomes.",
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AU - Ghadimi, Markus P.

AU - Liu, Ping

AU - Peng, Tingsheng

AU - Bolshakov, Svetlana

AU - Young, Eric D.

AU - Torres, Keila E.

AU - Colombo, Chiara

AU - Hoffman, Aviad

AU - Broccoli, Dominique

AU - Hornick, Jason L.

AU - Lazar, Alexander J.

AU - Pisters, Peter

AU - Pollock, Raphael E.

AU - Lev, Dina

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N2 - BACKGROUND: Pleomorphic liposarcoma (PLS) is a rare high-grade sarcoma that has lipoblastic differentiation. In this study, the authors evaluated PLS natural history, patient outcomes, and commonly deregulated protein biomarkers. METHODS: Medical records from patients (n = 155) who had PLS from 1993 to 2010 were reviewed. Univariate and multivariate analyses were conducted to identify independent prognosticators. A PLS tissue microarray (TMA) (n = 56 patient specimens) was constructed for immunohistochemical analysis of molecular markers, and p53 gene sequencing (exons 5-9) was conducted. RESULTS: The average patient age was 57 years, and the patients presented with primary disease (n = 102), recurrent disease (n = 16), and metastatic disease (n = 37). Lower extremity was the most common disease site (40%), and the average tumor size was 11 cm. Complete follow-up data were available for 83 patients, and their median follow-up was 22.6 months. The 5-year disease-specific survival rate was 53%; and recurrent disease, unresectability, and microscopic positive margins were identified as predictors of a poor prognosis. Systemic relapse (the strongest poor prognostic determinant) developed in 35% of patients with localized PLS. Immunohistochemical analysis revealed increased expression of peroxisome proliferator-activated receptor gamma (an adipogenic marker), B-cell leukemia 2 and survivin (survival factors), vascular endothelial growth factor (an angiogenic factor), matrix metalloproteinase 2, and other biomarkers. Frequent loss of retinoblastoma protein expression and high p53 mutation rates (approximately 60%) were observed. CONCLUSIONS: PLS is an aggressive, metastasizing sarcoma. Identifying ubiquitous molecular events underlying PLS progression is crucial for progress in patient management and outcomes.

AB - BACKGROUND: Pleomorphic liposarcoma (PLS) is a rare high-grade sarcoma that has lipoblastic differentiation. In this study, the authors evaluated PLS natural history, patient outcomes, and commonly deregulated protein biomarkers. METHODS: Medical records from patients (n = 155) who had PLS from 1993 to 2010 were reviewed. Univariate and multivariate analyses were conducted to identify independent prognosticators. A PLS tissue microarray (TMA) (n = 56 patient specimens) was constructed for immunohistochemical analysis of molecular markers, and p53 gene sequencing (exons 5-9) was conducted. RESULTS: The average patient age was 57 years, and the patients presented with primary disease (n = 102), recurrent disease (n = 16), and metastatic disease (n = 37). Lower extremity was the most common disease site (40%), and the average tumor size was 11 cm. Complete follow-up data were available for 83 patients, and their median follow-up was 22.6 months. The 5-year disease-specific survival rate was 53%; and recurrent disease, unresectability, and microscopic positive margins were identified as predictors of a poor prognosis. Systemic relapse (the strongest poor prognostic determinant) developed in 35% of patients with localized PLS. Immunohistochemical analysis revealed increased expression of peroxisome proliferator-activated receptor gamma (an adipogenic marker), B-cell leukemia 2 and survivin (survival factors), vascular endothelial growth factor (an angiogenic factor), matrix metalloproteinase 2, and other biomarkers. Frequent loss of retinoblastoma protein expression and high p53 mutation rates (approximately 60%) were observed. CONCLUSIONS: PLS is an aggressive, metastasizing sarcoma. Identifying ubiquitous molecular events underlying PLS progression is crucial for progress in patient management and outcomes.

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