Distinct profiles of oxidative stress-related and matrix proteins in adult bone and soft tissue osteosarcoma and desmoid tumors: a proteomics study.
Osteosarcomas rarely occur in older adults. Proteomics has not been reported to date in osteosarcoma occurring in the older adult population. This proteomic investigation was conducted to identify differentially expressed proteins in osteosarcoma occurring in various backgrounds from older adults. Desmoid tumors, known to recur locally but not metastasize, were also analyzed. Protein digests isolated from formalin-fixed, paraffin-embedded tumor tissue specimen representing 14 primary osteosarcomas of soft tissue and bone and 18 desmoid tumors were analyzed by high-resolution liquid chromatography-tandem mass spectrometry for protein identification and relative quantification by spectral counting. Elevated abundance levels of several proteins including heat shock protein 90 (HSP90), elastin microfibril interface-located protein 1, and clusterin were identified in osteosarcoma with slight differences in proteomic profiles. Desmoids had an abundance of collagen II and periostin only. The findings were confirmed by immunohistochemical staining for HSP90 and clusterin in the experimental samples and additionally in 16 posttherapy conventional osteosarcomas in tissue microarrays constructed from heterogeneous sarcomas and benign lesions. All osteosarcomas were positive for HSP90 and clusterin to a variable extent. One case of well-differentiated parosteal osteosarcoma was negative. Thirty of 75 other high-grade sarcomas including cases of chondrosarcoma were positive for HSP90. Low-grade and benign lesions and scars and 18 desmoid tumors had little or no expression of these proteins. HSP90 and clusterin represent candidate markers of aggressiveness in osteosarcoma occurring in older adults and may be indicative of drug resistance.
Department of Pathology, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian/Shadyside Hospitals, Pittsburgh, PA 15232, USA. raounm@upmc.edu
Uma N M
UN
Rao
Brian L
BL
Hood
Jacqueline M
JM
Jones-Laughner
Mai
M
Sun
Thomas P
TP
Conrads
D000008:Abdominal Neoplasms / Q000235:genetics / Q000378:metabolism*; D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D051152:Clusterin / Q000378:metabolism; D005260:Female; D018222:Desmoid Tumors / Q000235:genetics / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics*; D040901:Proteomics; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; C495242:CLU protein, human; D015815:Cell Adhesion Molecules; D051152:Clusterin; D018841:HSP90 Heat-Shock Proteins; C512835:POSTN protein, human