title: Predicting dedifferentiation in liposarcoma: a proteomic approach.
abstract: There are no known morphologic characteristics, cytogenetic aberrations, or molecular alterations predictive of dedifferentiation in liposarcomas. Identification of such a prognostic marker could potentially affect surgical and adjuvant therapy and/or follow-up surveillance for these patients. Two-dimensional difference gel electrophoresis was utilized to characterize protein expression patterns in lipoma, atypical lipomatous tumor (ALT), and the well-differentiated components of dedifferentiated liposarcoma (DDL). Protein spots were identified by peptide mapping/fingerprinting using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. No significant differences in protein expression were identified between lipoma and ALT or DDL. Proteins that were significantly down-regulated in the well-differentiated component of DDL compared to ALT included mitochondrial aldehyde dehydrogenase 2 (ALDH2, >3-fold reduction) and selenium-binding protein-1 (SELENBP1, >4-fold reduction). Subsequent validation studies were performed by immunohistochemistry (IHC) on a separate series of ALT (n = 30) and the well-differentiated components of DDL (n = 28). IHC stains were evaluated in a semi-quantitative manner, and the results were analyzed using the Mann-Whitney test and receiver-operator curve analysis. Decreased IHC staining for SELENBP1 in the well-differentiated component of DDL was confirmed. Cytoplasmic ALDH2 levels determined by IHC were not significantly different in ALT and DDL; no nuclear staining for ALDH2 was observed. Expression of SELENBP1 is decreased in the well-differentiated component of DDL compared to ALT. However, variability in the staining patterns in liposarcoma precludes its use as a predictive marker for dedifferentiation.
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, 1161 21st Ave. South, Nashville, TN 37232, USA.
authors.forename: Colt M
authors.initials: CM
authors.lastname: McClain
authors.forename: David B
authors.initials: DB
authors.lastname: Friedman
authors.forename: Tahar
authors.initials: T
authors.lastname: Hajri
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Coffin
authors.forename: Justin M M
authors.initials: JM
authors.lastname: Cates
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000444:Aldehyde Dehydrogenase / Q000032:analysis; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D054337:Cell Dedifferentiation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008080:Liposarcoma / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D051137:Selenium-Binding Proteins / Q000032:analysis; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: C495175:SELENBP1 protein, human; D051137:Selenium-Binding Proteins; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial