[64] Mesenteric and Superficial Fibromatosis Are Distinctly Different Tumors. A Proteomic Analysis Using Laser Microdissection and Mass Spectrophotometry

Alexandra Papova-Butler, John P Shapiro, Kari B Green, Michael A Freitas, Obiajulu H Iwenofu. OSUMC, Columbus, OH

Background: Mesenteric fibromatosis (a variant of deep fibromatosis) are locally aggressive clonal fibroblastic proliferations due to dysregulation of the Wnt/beta-catenin signalling pathway. Superficial fibromatosis exhibits striking histomorphologic and immunophenotypic overlap but genetically lack beta-catenin and APC mutations that are frequently seen in mesenteric fibromatosis. The biology of these tumors are also different. In this study, using archival formalin fixed paraffin embedded (FFPE) material, laser microdissection (LCM) and mass spectrophotometry were performed and the proteomics of these two disparate lesions in tandem with normal dermal collagen and scar tissue were evaluated.
Design: FFPE Archival material of superficial fibromatosis (SF, n=4), mesenteric fibromatosis (MF, n=4) Scar (n=4) and normal dermal collagen (DC, n=4) were retrieved from the OSU tissue archives. The diagnoses were validated and areas of interest were marked as a guide for LCM. Laser capture was performed using a Zeiss Palm Microbeam on 10um sections of tissues. The microdissected tissues were then digested with trypsin and analyzed using a high-resolution LTQ-Orbitrap tandem mass spectrometer. Data were analyzed using Matrix Science Mascot database search software.
Results: Comparison of the SF and MF revealed unique protein expression differences: Complement C3, C4 and Immunoglobins were upregulated in the MF compared to SF, indicating a possible immune mechanism. Tenascin and Collagen alpha-1were upregulated in SF. Ingenuity Pathway analysis of the data showed depletion in protein involved in Actin cytoskeletal signaling in the MF. The SF showed enrichment of proteins associated with acute phase response and ILK signaling. LMPC proteomics of scar vs normal DC showed significant differences in protein expression. Many more protein changes were seen in the SF and MF vs. normal comparisons. For MF, we observed downregulation of collagen alpha-1. Upregulated proteins included Myosin 10, Cytoskeleton-associated protein 4, complement C3, Serpin H1 and Perostin. SF vs DC showed downregulation of Decorin, alpha-2_macroglobulin and Prolargin. Proteins that were upregulated included Perostin and Tenascin.
Conclusions: Our data shows distinct clustering of differentially expressed proteins in MF and SF, supporting their molecular genetic differences. The differentially expressed proteins require further evaluation and validation as potential biomarkers and/or therapeutic targets.
Category: Bone & Soft Tissue

Monday, March 19, 2012 1:00 PM

Poster Session II # 29, Monday Afternoon


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