title: KRAS, EGFR, PDGFR-α, KIT and COX-2 status in carcinoma showing thymus-like elements (CASTLE).
abstract: BACKGROUND
  CASTLE (Carcinoma showing thymus-like elements) is a rare malignant neoplasm of the thyroid resembling lymphoepithelioma-like and squamous cell carcinoma of the thymus with different biological behaviour and a better prognosis than anaplastic carcinoma of the thyroid.
  
  
  METHODS
  We retrospectively investigated 6 cases of this very rare neoplasm in order to investigate the mutational status of KRAS, EGFR, PDGFR-α and KIT, as well as the immunohistochemical expression pattern of CD117, EGFR and COX-2, and possibly find new therapeutic targets.
  
  
  RESULTS
  Diagnosis was confirmed by a moderate to strong expression of CD5, CD117 and CK5/6, whereas thyroglobulin, calcitonin and TTF-1 were negative in all cases. Tumors were also positive for COX-2 and in nearly all cases for EGFR. In four cases single nucleotide polymorphisms (SNPs) could be detected in exon 12 of the PDGFR-α gene (rs1873778), in three cases SNPs were found in exon 20 of the EGFR gene (rs1050171). No mutations were found in the KIT and KRAS gene.
  
  
  CONCLUSIONS
  All tumors showed a COX-2 expression as well as an EGFR expression except for one case and a wild-type KRAS status. No activating mutations in the EGFR, KIT and PDGFR-α gene could be detected. Our data may indicate a potential for targeted therapies, but if these therapeutic strategies are of benefit in CASTLE remains to be determined.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1658499296115016.
authors.affiliation: Institute of Pathology, Klinikum Bayreuth, Preuschwitzerstraße 101, Bayreuth 95445, Germany. Lothar.Veits@klinikum-bayreuth.de.
authors.forename: Lothar
authors.initials: L
authors.lastname: Veits
authors.forename: Rupert
authors.initials: R
authors.lastname: Schupfner
authors.forename: Petra
authors.initials: P
authors.lastname: Hufnagel
authors.forename: Roland
authors.initials: R
authors.lastname: Penzel
authors.forename: Jens
authors.initials: J
authors.lastname: Freitag
authors.forename: Philipp
authors.initials: P
authors.lastname: Ströbel
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kern
authors.forename: Sören
authors.initials: S
authors.lastname: Schröder
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Neuhold
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Schmid
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Rieker
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002277:Carcinoma / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D051546:Cyclooxygenase 2 / Q000032:analysis*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins