Comparative Proteomic Analysis of Uterine Leiomyomas and Leiomyosarcomas.
Giuliana A Trucco, Brian L Hood, Thomas P Conrads, Jacqueline M Jones-Laughner, Mai Sun, Mirka W Jones. UMPC/Magee Womens Hospital/University of Pittsburgh, PA; University of Pittsburgh Cancer Institute/Magee Womens Research Institute, PA
Background: Proteomics confirm the presence of different proteins in normal tissues and tumors and provide a direct measure of the quantity present. By identifying proteins associated with a malignant process proteomics provide the information how to interfere with the action of those proteins and how to find a drug that may inactivate that action.
We compared protein expression in uterine leiomyomas (LM) and leiomyosarcomas (LMS) in search for targets related to histologic features of malignancy and an aggressive behavior.
Design: The IRB approved study included 14 LMS and 14 LM, identified in our file between 2002 and 2006. The selected formalin-fixed paraffin-embedded tissues were processed using a heat-induced / enzyme-mediated digestion methodology and analyzed in triplicate by LC-MS/MS on a linear ion trap mass spectrometer. Tandem mass spectra were searched against the UniProt human protein database and differences in protein abundance between the samples were derived by summing the total CID events that resulted in a positively identified peptide for a given protein accession across all samples (spectral counting). The spectral count data were normalized for each protein accession by calculating the percent contribution of the spectral count values for each protein accession against the total number of peptides identified within a given sample.
Results: The tumor samples were tested for the presence of 216 proteins and 39 were detected using stringency criteria based on an 80% population of samples with two or more peptides for identifications. Out of 16 proteins that show statistically significant up-regulated expression in LMS compared to LM, the following are known to be associated with malignancies: 60S acidic ribosomal protein P1, Ezrin, Fructose-bisphosphate aldolase A, Isoform 1 of Heterogeneous nuclear ribonucleoprotein K, Lamin-B1, Protein disulfide-isomerase, Tubulin alpha-1A chain. Of the 11 proteins showing statistically significant down-regulated expression, some (Actin, Alpha-actinin-1, Isoform 1 of Filamin-A, Isoform 1 of Sorbin and SH3 domain-containing protein 1, Transgelin) appear also to be associated with malignancies.
Conclusions: The statistically significant difference in expression of various proteins between LMS and LM may aid the histologic evaluation of smooth muscle tumors and help to identify tumors with more aggressive behavior. In addition the proteomic analysis may lead to a potential identification of a new treatment.
Category: Gynecologic & Obstetrics
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 187, Wednesday Afternoon