title: Cyclooxygenase-2 expression in pediatric sarcomas.
abstract: Therapies for metastatic pediatric sarcomas have reached maximum tolerated doses, but continue to provide suboptimal cure rates. Additionally, these treatments are associated with numerous short- and long-term side effects. Therefore, the search for newer, less toxic therapeutic agents is warranted. Overexpression of the inducible enzyme, cyclooxygenase-2 (COX-2), has been discovered in a variety of adult solid tumors and numerous studies have shown COX-2 inhibitors to have significant antiproliferative effects. Therefore, we sought to determine the expression of COX-2 in pediatric sarcomas. We evaluated rhabdomyosarcoma (RMS), osteosarcoma (OS), and Ewing sarcoma (EWS) samples for COX-2 expression by immunohistochemical analysis as well as by cDNA microarray analysis. COX-2 expression was detected in 48/58 (82.8%) tumors by immunohistochemistry and in an additional 52/59 (88.1%) tumors tested by microarray gene analysis. There was a trend toward increased COX-2 expression in metastatic rhabdomyosarcoma and osteosarcoma, though it did not reach clinical significance. The degree of COX-2 immunoreactivity did not vary significantly with other clinicopathologic features such as age, gender, or histologic classification. We conclude that the majority of these pediatric sarcoma samples express COX-2 to varying degrees. Therefore, studies testing the efficacy of COX-2 inhibitors in the treatment of pediatric sarcomas are warranted.
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. dicq3z@chmc.org
authors.forename: David S
authors.initials: DS
authors.lastname: Dickens
authors.forename: Rafal
authors.initials: R
authors.lastname: Kozielski
authors.forename: Javed
authors.initials: J
authors.lastname: Khan
authors.forename: Anne
authors.initials: A
authors.lastname: Forus
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Cripe
mesh_terms: D000293:Adolescent; D001859:Bone Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002648:Child; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D020411:Oligonucleotide Array Sequence Analysis; D012516:Osteosarcoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012208:Rhabdomyosarcoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D012509:Sarcoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012512:Sarcoma, Ewing / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases