Ossifying Fibromyxoid Tumor of Soft Parts (OFMT): A Clinicopathologic, Proteomic and Genomic Study.
Rondell P Graham, Sarah M Dry, Xinmin Li, Scott W Binder, Ahmet Dogan, Andrew L Folpe. Mayo Clinic, Rochester, MN; UCLA, Los Angeles, CA
Background: OFMT, rare neoplasms of uncertain differentiation, are usually histologically and clinically benign. However, some OFMT are histologically malignant and aggressive, and the behavior of all OFMT may be unpredictable. We studied the clinicopathological features of a large series of OFMT and performed paraffin section proteomic and DNA microarray studies, to more fully elucidate their behavior and differentiation.
Design: 38 OFMT were retrieved and classified as "typical" (OFMT-T), "atypical" (OFMT-AT) and "malignant" (OFMT-M) using published criteria. Follow-up (F/U) was obtained. For proteomics, formalin-fixed, paraffin-embedded (FFPE) blocks from 5 OFMT-T were microdissected, trypsin digested, and analyzed by mass spectrometry. Data was correlated to fragmentation patterns of peptide sequences (Swissprot database). For genomics, total RNA was isolated from FFPE blocks of 7 OFMT-T and hybridized to the Affymetrix Human U133plus 2.0 Array. AGCC imaging software and Partek Genomics Suite Version 6.4 were used.
Results: OFMT-T (N=19) occurred in 10M/9F (median 51 yrs) in various soft tissue (ST) locations (median size 3 cm, range 1.1-11 cm). OFMT-AT (N=8) occurred in 5M/3F (median 43 yrs) in diverse ST locations (median size 3.2 cm, range 1.5-8.5 cm). OFMT-M (N=11)occurred in 10M/9F (median 51 yrs) in varied ST locations (median size 3 cm, range 1-11 cm). Clinical f/u >12 mos was available for 10/19 OFMT-T (median 51 mos, range 12-149 mos), 2/8 OFMT-AT (66 and 131 mos) and 7/11 OFMT-M (median 22 mos, range 12-100 mos). All OFMT-T and OFMT-AT with F/U were alive without disease. For OFMT-M with F/U, 4 were without disease, 1 was alive with local recurrence (LR), and 2 were dead of disease, with LR and metastases. Proteomic results included abundant collagens 1A2, 1 A1 and 6A3 and S-100 protein; collagen II (cartilage) was absent. Genomic results showed OFMT to be distinct from nerve sheath tumors, with high level expression of neuron-associated genes, including HuC and SLC1A3, and low levels of schwann cell and/or cartilage associated genes, including PMP22.
Conclusions: The results of this, the first proteonomic and genomic study of OFMT, suggest that these rare, enigmatic tumors differentiate along neuronal, rather than schwannian or cartilaginous lines, as has been previously suggested. On-going immunohistochemical studies should help to validate these results in larger numbers of cases. Our study confirms the validity of the current classification of OFMT, with clinically malignant behavior being seen only in OFMT-M, but not in OFMT-T or OFMT-AT.
Category: Bone & Soft Tissue
Monday, February 28, 2011 8:30 AM
Platform Session: Section F, Monday Morning