Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases

Heid, Hans; Moll, Roland; Schwetlick, Ina; Rackwitz, Hans-Richard; Keenan, T.W.

doi:10.1007/s004410051181

Cited by 393 publications

(361 citation statements)

References 42 publications

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“…All samples expressed high levels of adipophilin, a known marker of adipogenesis that appears early in the differentiation process, 21 perhaps suggesting that both MLS tumors and RCL tumors differentiate beyond the initial stage(s) before the disruption of complete adipocytic maturation. Moreover, we observed significantly higher levels of adipophilin in RCL tumors versus MLS tumors, perhaps suggesting that adipophilin participates in disease progression.…”

Section: Myxoid/round Cell Liposarcoma-related Biomarkersmentioning

confidence: 99%

Localized and metastatic myxoid/round cell liposarcoma

Hoffman

Ghadimi

Demicco

et al. 2013

Cancer

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BACKGROUND. Myxoid liposarcoma (MLPS), a disease especially of young adults with potential for local recurrence and metastasis, currently lacks solid prognostic factors and therapeutic targets. The authors of this report evaluated the natural history and outcome of patients with MLPS and commonly deregulated protein biomarkers. METHODS. Medical records were retrospectively reviewed for patients who presented to the authors' institution with localized (n ¼ 207) or metastatic (n ¼ 61) MLPS (1990MLPS ( to 2010. A tissue microarray of MLPS patient specimens (n ¼ 169) was constructed for immunohistochemical analysis of molecular markers. RESULTS. The 5-year and 10-year disease-specific survival rates among patients with localized disease were 93% and 87%, respectively; male gender, age >45 years, and recurrent tumor predicted poor outcome. The local recurrence rate was 7.4%, and the risk of local recurrence was associated with recurrent tumors and nonextremity disease location. Male gender was the main risk factor for metastatic disease, which occurred in 13% of patients. Forty percent of patients who had localized disease received chemotherapy, mostly in the neoadjuvant setting. Immunohistochemical analysis revealed significantly higher expression of C-X-C chemokine receptor type 4 (CXCR4) and platelet-derived growth factor beta (PDGFR-b) in metastatic lesions versus localized lesions. Tumors with a round cell phenotype expressed increased levels of CXCR4, p53, adipophilin, PDGFR-a, PDGFR-b, and vascular endothelial growth factor relative to myxoid phenotype. Only the receptor tyrosine kinase encoded by the AXL gene (AXL) was identified as a prognosticator of disease-specific survival in univariate analysis. CONCLUSIONS. In this study, the authors identified clinical and molecular outcome prognosticators for patients with MLPS as well as several potential therapeutic targets.

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Section: Myxoid/round Cell Liposarcoma-related Biomarkersmentioning

confidence: 99%

Localized and metastatic myxoid/round cell liposarcoma

Hoffman

Ghadimi

Demicco

et al. 2013

Cancer

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“…ADFP is expressed in many cell types and is associated with intracellular neutral lipid droplets (34). The precise relationship between ADFP and lipid droplet biology is still obscure (35,36).…”

Section: Genes Uniquely Regulated By Ox-ldlmentioning

confidence: 99%

Oxidized LDL immune complexes and oxidized LDL differentially affect the expression of genes involved with inflammation and survival in human U937 monocytic cells

et al. 2009

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Objective-To compare the global effects of oxidized LDL (oxLDL) and oxLDL-containing immune complexes (oxLDL-IC) on gene expression in human monocytic cells and to identify differentially expressed genes involved with inflammation and survival.Methods and Results-U937 cells were treated with oxLDL-IC, oxLDL, Keyhole limpet hemocyanin immune complexes (KLH-IC), or vehicle for 4 h. Transcriptome profiling was performed using DNA microarrays. oxLDL-IC uniquely affected the expression of genes involved with pro-survival (RAD54B, RUFY3, SNRPB2, and ZBTB24). oxLDL-IC also regulated many genes in a manner similar to KLH-IC. Functional categorization of these genes revealed that 39% are involved with stress responses, including the unfolded protein response which impacts cell survival, 19% with regulation of transcription, 10% with endocytosis and intracellular transport of protein and lipid, and 16% with inflammatory responses including regulation of I-κB/NF-κB cascade and cytokine activity. One gene in particular, HSP70 6, greatly up-regulated by ox-LDL-IC, was found to be required for the process by which oxLDL-IC augments IL1-β secretion. The study also revealed genes uniquely up-regulated by oxLDL including genes involved with growth inhibition (OKL38, NEK3, and FTH1), oxidoreductase activity (SPXN1 and HMOX1), and transport of amino acids and fatty acids (SLC7A11 and ADFP).Conclusions-These findings highlight early transcriptional responses elicited by oxLDL-IC that may underlie its cytoprotective and pro-inflammatory effects. Cross-linking of Fcγ receptors appears to be the trigger for most of the transcriptional responses to oxLDL-IC. The findings further strengthen the hypothesis that oxLDL and oxLDL-IC elicit disparate inflammatory responses and play distinct roles in the process of atherosclerosis.

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“…17 Adipophilin is reported to be expressed in cells of lactating mammary epithelium, adrenal cortex, male reproductive system (Sertoli and Leydig cells), steatotic hepatocytes in alcoholic cirrhosis, and liposarcomas. 17,21 Mature adipocytes of fibroadipose tissue lack immunostaining for adipophilin. 21 Studies have shown these antibodies to be useful as ancillary studies to show intracellular lipid in sebaceous carcinoma.…”

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confidence: 99%

“…17,21 Mature adipocytes of fibroadipose tissue lack immunostaining for adipophilin. 21 Studies have shown these antibodies to be useful as ancillary studies to show intracellular lipid in sebaceous carcinoma. Although all three perilipin family antibodies had high specificity (adipophilin, 77%; perilipin, 100%; and TIP47/ PP17, 100%), adipophilin sensitivity (88.5%) was superior (perilipin, 45.5% and TIP47/PP17, 8.3%).…”

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confidence: 99%

Adipophilin expression in sebaceous tumors and other cutaneous lesions with clear cell histology: an immunohistochemical study of 117 cases

et al. 2010

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Adipophilin is a monoclonal antibody against a protein on the surface of intracellular lipid droplets, and it was recently shown to be expressed in sebocytes and sebaceous lesions. This study examines adipophilin expression in various sebaceous lesions and other cutaneous tumors with a clear cell histology that may mimic sebaceous differentiation. A total of 117 cutaneous clear cell lesions including 16 sebaceous adenomas, 25 sebaceous carcinomas, 8 basal cell carcinomas, 12 squamous cell carcinomas, 6 xanthomas, 10 xanthelasmas, 10 xanthogranulomas, 4 balloon cell nevi, 5 trichilemmomas, 8 clear cell hidradenomas, and 13 metastatic renal cell carcinomas were examined using immunohistochemistry for the expression of adipophilin. Of these 117 lesions, 42 (36%) were from the periocular region. Adipophilin was expressed in 16 of 16 (100%) sebaceous adenomas, 23 of 25 (92%) sebaceous carcinomas, 10 of 10 (100%) xanthelasmas, 9 of 10 (90%) xanthogranulomas, 6 of 6 (100%) xanthomas, and 9 of 13 (62.5%) metastatic renal cell carcinomas. The characteristic staining pattern differed between sebaceous and non-sebaceous tumors with the former showing a membranous vesicular pattern and the latter being more granular. Adipophilin expression was not seen in any of the other lesions with clear cell histology, basal cell carcinomas, or squamous cell carcinomas, including cases that had focal clear cell differentiation. Adipophilin can be valuable in an immunohistochemical panel when evaluating cutaneous lesions with clear cell histology as it identifies intracytoplasmic lipid vesicles in sebaceous and xanthomatous lesions. In periocular lesions, it is effective in helping to exclude basal cell carcinoma and squamous cell carcinoma when sebaceous carcinoma is under consideration. Adipophilin expression is not as useful for the differential diagnosis that includes metastatic renal cell carcinoma, a rare but important, diagnostic differential. The pattern of adipophilin reactivity is important to observe as membranous vesicular staining is suggestive of intracellular lipids whereas granular cytoplasmic reactivity is not. Modern Pathology (2010) 23, 567-573; doi:10.1038/modpathol.2010.1; published online 29 January 2010Keywords: adipophilin; sebaceous tumors; differential diagnosis Sebaceous carcinoma is a relatively uncommon tumor comprising 0.05% of all cutaneous malignancies, but is the second or third most common malignant eyelid tumor in most series accounting for 2-4% of periocular tumors. 1 Local recurrence complicates 6-29% of periocular sebaceous cell carcinomas. [2][3][4][5] Regional or distal metastases affect 14-25% of patients with an associated 5-year mortality ranging from 30 to 67% according to different reports. 2,4 Owing to its variable clinical appearance, sebaceous carcinoma mimics both benign processes, such as chalazions and blepharitis, and other malignant

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Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases

Cited by 393 publications

References 42 publications

Localized and metastatic myxoid/round cell liposarcoma

Localized and metastatic myxoid/round cell liposarcoma

Oxidized LDL immune complexes and oxidized LDL differentially affect the expression of genes involved with inflammation and survival in human U937 monocytic cells

Adipophilin expression in sebaceous tumors and other cutaneous lesions with clear cell histology: an immunohistochemical study of 117 cases

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