title: COX-2 upregulation in thymomas and thymic carcinomas.
abstract: The treatment of advanced stage thymomas and thymic carcinomas is a multimodal therapy. New therapeutic targets are currently under investigation, including the epidermal growth factor receptor (EGFR) as well as KIT. A number of studies have shown protumorigenic potential of Cyclooxygenase-2 (COX-2) in a variety of human malignancies, but so far it is unknown whether COX-2 is expressed in primary malignancies of the thymus. Using tissue microarrays, the expression of COX-2, microsomal-PGES-1 and -PGES-2 (mPGES-1 and mPGES-2), as well as EGFR was evaluated in different subtypes of thymoma and thymic carcinomas. COX-2 was expressed in all subtypes as determined by immunohistochemistry. Some cases of type B2 and thymic carcinomas had COX-2 staining levels classified as mild to moderate. However, when measuring the optical color intensity, no significant differences could be detected. Concerning the expression levels, a weak correlation between the expression of COX-2, mPGES-1 and mPGES-2 as well as EGFR was found. Furthermore, additional cases of thymomas and thymic carcinomas were analyzed by COX-2 Western immunoblot analysis and were compared to normal thymi. The analysis showed that thymomas and thymic carcinomas had a significantly stronger COX-2 expression than that of the normal thymi (p < 0.04). In summary, COX-2 is expressed in all subtypes of thymomas and thymic carcinomas and thus represents, in addition to EGFR and KIT, a potential therapeutic target. Further studies are needed in order to determine whether a combined therapy using COX-2 inhibitors in addition to the evolving anti-EGFR antibody therapy may be considered as a treatment option.
authors.affiliation: Department of General Pathology, University Hospital, Heidelberg, Germany. ralf.rieker@med.uni-heidelberg.de
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Rieker
authors.forename: Stefan
authors.initials: S
authors.lastname: Joos
authors.forename: Gunhild
authors.initials: G
authors.lastname: Mechtersheimer
authors.forename: Hendrik
authors.initials: H
authors.lastname: Blaeker
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Schnabel
authors.forename: Alicia
authors.initials: A
authors.lastname: Morresi-Hauf
authors.forename: Erich
authors.initials: E
authors.lastname: Hecker
authors.forename: Michael
authors.initials: M
authors.lastname: Thomas
authors.forename: Hendrik
authors.initials: H
authors.lastname: Dienemann
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kern
mesh_terms: D000328:Adult; D000368:Aged; D002648:Child; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D013945:Thymoma / Q000201:enzymology* / Q000473:pathology; D013953:Thymus Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D051546:Cyclooxygenase 2