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Predicting dedifferentiation in liposarcoma: a proteomic approach

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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.

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Acknowledgments

This work was funded by the Shelby L. Richter Memorial Research Award (JMMC) granted by the Sarcoma Foundation of America.

Conflict of interest

The authors declare that they have no financial relationship with the Sarcoma Foundation of America or other conflicts of interest.

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Authors and Affiliations

  1. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, 1161 21st Ave. South, Nashville, TN, 37232, USA

    Colt M. McClain, Cheryl M. Coffin & Justin M. M. Cates

  2. Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University Medical Center, Nashville, TN, USA

    David B. Friedman

  3. Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

    Tahar Hajri

Authors
  1. Colt M. McClain
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  2. David B. Friedman
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Correspondence to Justin M. M. Cates.

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Proteins differentially expressed in lipoma, atypical lipomatous tumor, and dedifferentiated liposarcoma determined by two-dimensional difference gel electrophoresis. (PDF 68 kb)

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McClain, C.M., Friedman, D.B., Hajri, T. et al. Predicting dedifferentiation in liposarcoma: a proteomic approach. Virchows Arch 463, 85–92 (2013). https://doi.org/10.1007/s00428-013-1416-2

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  • DOI: https://doi.org/10.1007/s00428-013-1416-2

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