Abstract
Purpose
Liposarcomas are the most common soft tissue sarcomas of adults. The identification of lipoblastic cells in soft tissue sarcomas is mandatory for the diagnosis of most subtypes of liposarcomas but may be difficult in conventional histology. The present study focuses on the expression and possible diagnostic impact of two PAT family proteins, perilipin 1/perilipin and perilipin 2/adipophilin in human liposarcomas.
Methods
Eighty-seven cases of liposarcomas and 30 cases of non-lipomatous sarcomas were investigated immunohistochemically for perilipin 1 and 2 using entire tissue sections. Statistical analyses were performed using appropriate tests.
Results
Most liposarcomas and non-lipomatous sarcomas displayed positivity for perilipin 2. In contrast, while more than two-thirds of liposarcomas presented perilipin 1 positivity, all non-lipomatous sarcomas studied were negative for this marker, with statistical significance (p < 0.001). Perilipin 1 expression increased with adipocytic differentiation of liposarcoma subtypes showing statistical significance (p < 0.001). Non-lipomatous sarcomas demonstrated variable expression levels of perilipin 2. The expression level of perilipin 2 appeared to be correlated with tumor cell degeneration, e.g., through hypoxia.
Conclusions
Perilipin 2 is not well suitable for distinction between liposarcomas and non-lipomatous sarcomas. However, perilipin 1 appeared to be a highly specific marker for liposarcoma and adipocytic differentiation in sarcomas with intermediate sensitivity.
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References
Bickel PE, Tansey JT, Welte MA (2009) PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores. Biochim Biophys Acta 1791(6):419–440. doi:10.1016/j.bbalip.2009.04.002
Brasaemle DL, Barber T, Wolins NE, Serrero G, Blanchette-Mackie EJ, Londos C (1997) Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein. J Lipid Res 38(11):2249–2263
Dabbs DJ (2014) Diagnostic immunohistochemistry: theranostic and genomic applications, 4th edn. Elsevier/Saunders, Philadelphia
Dei Tos AP (2014) Liposarcomas: diagnostic pitfalls and new insights. Histopathology 64(1):38–52. doi:10.1111/his.12311
Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (eds) (2013) WHO classification of tumours of soft tissue, 4th edn. World Health Organization Classification of Tumours, Lyon
Goldblum JR, Folpe AL, Weiss SW, Enzinger FM (2014) Enzinger and Weiss’s soft tissue tumors, 6th edn. Saunders/Elsevier, Philadelphia
Heid HW, Moll R, Schwetlick I, Rackwitz H-R, Keenan TW (1998) Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases. Cell Tissue Res 294(2):309–321. doi:10.1007/s004410051181
Heid H, Rickelt S, Zimbelmann R, Winter S, Schumacher H, Dorflinger Y (2013) Lipid droplets, perilipins and cytokeratins—unravelled liaisons in epithelium-derived cells. PLoS ONE 8(5):e63061. doi:10.1371/journal.pone.0063061
Heid H, Rickelt S, Zimbelmann R, Winter S, Schumacher H, Dorflinger Y, Kuhn C, Franke WW (2014) On the formation of lipid droplets in human adipocytes: the organization of the perilipin–vimentin cortex. PLoS ONE 9(2):e90386. doi:10.1371/journal.pone.0090386
Iwasaki H, Ishiguro M, Nishio J, Aoki M, Yokoyama R, Yokoyama K, Taguchi K, Nabeshima K (2015) Extensive lipoma-like changes of myxoid liposarcoma: morphologic, immunohistochemical, and molecular cytogenetic analyses. Virchows Arch 466(4):453–464. doi:10.1007/s00428-015-1721-z
Katenkamp D (2011) Histological classification of soft tissue tumors and staging according to the TNM system (Histologische Klassifikation von Weichgewebstumoren und Stadieneinteilung gemass TNM-System). Pathologe 32(1):8–13. doi:10.1007/s00292-010-1391-1
Kimmel AR, Brasaemle DL, McAndrews-Hill M, Sztalryd C, Londos C (2010) Adoption of PERILIPIN as a unifying nomenclature for the mammalian PAT-family of intracellular lipid storage droplet proteins. J Lipid Res 51(3):468–471. doi:10.1194/jlr.R000034
Menendez JA, Lupu R (2007) Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 7(10):763–777. doi:10.1038/nrc2222
Mrozinski J, Schwetlick I, Heid HW, Winter-Simanowski S, Holzbach A, Hinze R, Franke WW, Moll R (1999) Adipophilin and perilipin, two lipid-droplet-associated proteins, in the pathohistological differential diagnosis of human soft tissue sarcomas. P14. J Cancer Res Clin Oncol 125(Suppl):S48–S49
Olsen AM, Eisenberg BL, Kuemmerle NB, Flanagan AJ, Morganelli PM, Lombardo PS, Swinnen JV, Kinlaw WB (2010) Fatty acid synthesis is a therapeutic target in human liposarcoma. Int J Oncol 36(5):1309–1314
Pandey PR, Liu W, Xing F, Fukuda K, Watabe K (2012) Anti-cancer drugs targeting fatty acid synthase (FAS). Recent Pat Anticancer Drug Discov 7(2):185–197
Patel AV, Johansson G, Colbert MC, Dasgupta B, Ratner N (2015) Fatty acid synthase is a metabolic oncogene targetable in malignant peripheral nerve sheath tumors. Neuro Oncol 17(12):1599–1608. doi:10.1093/neuonc/nov076
Pawella LM, Hashani M, Eiteneuer E, Renner M, Bartenschlager R, Schirmacher P, Straub BK (2014) Perilipin discerns chronic from acute hepatocellular steatosis. J Hepatol 60(3):633–642. doi:10.1016/j.jhep.2013.11.007
R Development Core Team (2008) R: A language and environment for statistical computing. Austria, Vienna
Straub BK, Stoeffel P, Heid H, Zimbelmann R, Schirmacher P (2008) Differential pattern of lipid droplet-associated proteins and de novo perilipin expression in hepatocyte steatogenesis. Hepatology 47(6):1936–1946. doi:10.1002/hep.22268
Straub BK, Herpel E, Singer S, Zimbelmann R, Breuhahn K, Macher-Goeppinger S, Warth A, Lehmann-Koch J, Longerich T, Heid H, Schirmacher P (2010) Lipid droplet-associated PAT-proteins show frequent and differential expression in neoplastic steatogenesis. Mod Pathol 23(3):480–492. doi:10.1038/modpathol.2009.191
Straub BK, Gyoengyoesi B, Koenig M, Hashani M, Pawella LM, Herpel E, Mueller W, Macher-Goeppinger S, Heid H, Schirmacher P (2013) Adipophilin/perilipin-2 as a lipid droplet-specific marker for metabolically active cells and diseases associated with metabolic dysregulation. Histopathology 62(4):617–631. doi:10.1111/his.12038
Subirana I, Sanz H, Vila J (2014) Building bivariate tables: the compareGroups package for R. J Stat Softw 57(12):1–16
Suresh TN, Harendra Kumar ML, Prasad CS, Kalyani R, Borappa K (2009) Malignant peripheral nerve sheath tumor with divergent differentiation. Indian J Pathol Microbiol 52(1):74. doi:10.4103/0377-4929.44971
Sztalryd C, Kimmel AR (2014) Perilipins: lipid droplet coat proteins adapted for tissue-specific energy storage and utilization, and lipid cytoprotection. Biochimie 96:96–101. doi:10.1016/j.biochi.2013.08.026
Wang X, Reape TJ, Li X, Rayner K, Webb CL, Burnand KG, Lysko PG (1999) Induced expression of adipophilin mRNA in human macrophages stimulated with oxidized low-density lipoprotein and in atherosclerotic lesions. FEBS Lett 462(1–2):145–150. doi:10.1016/S0014-5793(99)01521-5
Acknowledgments
We thank Stefanie Winter-Simanowski, Anke Holzbach-Röper and Viktoria Wischmann for expert technical assistance. Dr. Raoul Hinze (Martin Luther University of Halle-Wittenberg, Institute of Pathology, Halle/Saale, present address HELIOS Clinics, Institute of Pathology, Schwerin) was of great help with the recruitment of cases. We also thank Hanna Daniel (Philipps University of Marburg, Institute of Medical Biometry and Epidemiology, Marburg) for helpful advice and comments regarding the statistical analysis and Prof. Dr. Werner W. Franke (Helmholtz Group for Cell Biology, German Cancer Research Center, Heidelberg) for continuous support. CCW is supported by the postdoctoral lecture qualification program of the Anneliese Pohl Foundation, Marburg.
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The work was funded by Philipps University of Marburg, Marburg, Germany.
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All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Concerning the use of human material, the study was approved by the Ethics Committee of the Medical Faculty of the Philipps University of Marburg. This article does not contain any studies with animals performed by any of the authors.
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Westhoff, C.C., Mrozinski, J., Riedel, I. et al. Perilipin 1 is a highly specific marker for adipocytic differentiation in sarcomas with intermediate sensitivity. J Cancer Res Clin Oncol 143, 225–232 (2017). https://doi.org/10.1007/s00432-016-2263-8
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DOI: https://doi.org/10.1007/s00432-016-2263-8