PMID- 21997683 OWN - NLM STAT- MEDLINE DCOM- 20111207 LR - 20220331 IS - 1532-0979 (Electronic) IS - 0147-5185 (Print) IS - 0147-5185 (Linking) VI - 35 IP - 11 DP - 2011 Nov TI - Ossifying fibromyxoid tumor of soft parts: a clinicopathologic, proteomic, and genomic study. PG - 1615-25 LID - 10.1097/PAS.0b013e3182284a3f [doi] AB - Ossifying fibromyxoid tumor (OFMTs) of soft parts is a rare soft tissue and bone tumor of borderline malignancy displaying an uncertain line of differentiation. The existence of fully malignant OFMT is controversial. To better understand the natural history and line of differentiation taken by OFMT, we studied 46 cases by light microscopic, immunohistochemical (IHC), genomic, proteomic, and fluorescence in situ hybridization (FISH) methods. Cases were classified according to the 2003 Folpe and Weiss system. Clinical and follow-up information was obtained. IHC for S-100 protein, desmin, epithelial membrane antigen (EMA), cytokeratins, smooth muscle actin (SMA), INI-1, neurofilament protein (NFP), CD56d excitatory amino acid transporter-4 (EAAT4), and MUC4 was performed on formalin-fixed, paraffin-embedded (FFPE) tissues. Gene expression profiling and proteomic studies were conducted on FFPE tissues from 13 and 5 cases, respectively. FISH for INI-1 was performed on 10 cases. The 46 tumors arose in 29 men and 17 women (median age, 52 y; range 39 to 63 y) and involved the proximal (N=17) and distal extremities (N=13), head and neck (N=9), and trunk (N=5). Median tumor size was 5.4 cm (range, 1.0 to 21.0 cm). Cases were classified as typical OFMT (26 of 46, 57%), atypical OFMT (5 of 46, 11%), and malignant OFMT (15 of 46 cases, 32%). Clinical follow-up (27 cases, median 55 months' duration) showed all patients with typical and atypical OFMT to be alive without disease. Adverse events, including 3 local recurrences, 3 metastases, and 3 deaths, were seen only in malignant OFMT. IHC results were as follows: S-100 protein (30 of 41, 73%), desmin (15 of 39, 38%), cytokeratin (4 of 35, 11%), EMA (5 of 32, 16%), SMA (2 of 34, 6%), INI-1 (lost in mosaic pattern in 14 of 19, 74%), EAAT4 (31 of 39, 80%), MUC4 (3 of 14, 21%), NFP (8 of 10, 80%) and CD56 (6 of 14, 43%). Gene expression profiling showed typical and malignant OFMTs to cluster together, distinct from schwannian tumors. Proteomic study showed expression of various collagens, S-100 protein, and neuron-related proteins. FISH showed INI-1 deletion in 5 of 7 (71%) cases. We conclude that malignant OFMTs exist and may be recognized by the previously proposed criteria of Folpe and Weiss. Expression of neuron-related markers, in addition to Schwann cell and cartilage-associated markers, suggests a "scrambled" phenotype in OFMTs. Loss of INI-1 or other genes on 22q is likely important in the pathogenesis of these rare tumors. FAU - Graham, Rondell P D AU - Graham RP AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA. FAU - Dry, Sarah AU - Dry S FAU - Li, Xinmin AU - Li X FAU - Binder, Scott AU - Binder S FAU - Bahrami, Armita AU - Bahrami A FAU - Raimondi, Susana C AU - Raimondi SC FAU - Dogan, Ahmet AU - Dogan A FAU - Chakraborty, Subhankar AU - Chakraborty S FAU - Souchek, Joshua J AU - Souchek JJ FAU - Folpe, Andrew L AU - Folpe AL LA - eng GR - T32 CA009476-21/CA/NCI NIH HHS/United States GR - CA 09476/CA/NCI NIH HHS/United States GR - CA 78590/CA/NCI NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PL - United States TA - Am J Surg Pathol JT - The American journal of surgical pathology JID - 7707904 RN - 0 (Biomarkers, Tumor) SB - IM MH - Adult MH - *Biomarkers, Tumor/analysis/genetics MH - Biopsy MH - Chromatography, Liquid MH - Female MH - *Fibroma, Ossifying/chemistry/genetics/pathology MH - Gene Expression Profiling MH - *Gene Expression Regulation, Neoplastic MH - *Genomics/methods MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Prognosis MH - *Proteomics/methods MH - *Soft Tissue Neoplasms/chemistry/genetics/pathology MH - Spectrometry, Mass, Electrospray Ionization MH - Tandem Mass Spectrometry MH - United States PMC - PMC3193600 MID - NIHMS310555 EDAT- 2011/10/15 06:00 MHDA- 2011/12/13 00:00 PMCR- 2012/11/01 CRDT- 2011/10/15 06:00 PHST- 2011/10/15 06:00 [entrez] PHST- 2011/10/15 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] PHST- 2012/11/01 00:00 [pmc-release] AID - 00000478-201111000-00002 [pii] AID - 10.1097/PAS.0b013e3182284a3f [doi] PST - ppublish SO - Am J Surg Pathol. 2011 Nov;35(11):1615-25. doi: 10.1097/PAS.0b013e3182284a3f.