title: Pattern of TGFbeta receptor 1 expression differs between kras-mutated keratoacanthomas and squamous cell carcinomas of the skin.
abstract: OBJECTIVE
  Increasing evidence indicates that TGFbeta- and EGFR-signaling is involved in the pathogenesis of keratoacanthoma (KA) and squamous cell carcinoma (SCC) of the skin. We analyzed the expression pattern of TGFbeta-signaling components and screened for mutations in tgfbetaR1, egfr, kras and braf in KAs and SCCs.
  
  
  METHODS
  Immunohistochemical analysis of TGFbeta1, TGFbetaR1, TGFbetaR2 and phospho-SMAD2/3 was performed on skin tumors (29 KAs, 30 well and 31 moderately differentiated SCCs). Mutation screening in hotspot regions of tgfbetaR1, egfr, kras and braf was performed through pyrosequencing of tumor DNA.
  
  
  RESULTS
  Expression of TGFbeta1, TGFbetaR1 and p-SMAD2/3 was increased in tumors as compared to surrounding skin. In KAs characteristic strong discontinuous membranous TGFbetaR1 expression pattern frequently associated with kras mutation was noted. SCCs showed continuous TGFbetaR1 expression, stronger p-SMAD2/3 expression and less frequent kras mutations. In tumors at sun-exposed sites stronger TGFbetaR1 expression was noted. One SCC showed tgfbetaR1 mutation, but no other mutations were found.
  
  
  CONCLUSIONS
  Although tgfbetaR1 germline mutations cause inherited KAs and our finding of strong discontinuous membranous expression in KAs suggests accumulation of functionally altered protein, we found no tgfbetaR1 mutations or influence on TGFbeta-signaling, but frequent kras mutations in this subgroup of KAs. Characteristic TGFbetaR1 expression pattern in KA can facilitate histopathologic distinction from SCC.
authors: Institute of Pathology, St. Vincentius Hospital Karlsruhe, Germany.
authors: Franziska
authors: F
authors: Berger
authors: Institute of Pathology, St. Vincentius Hospital Karlsruhe, Germany.
authors: Helene
authors: H
authors: Geddert
authors: Institute of Pathology, St. Vincentius Hospital Karlsruhe, Germany.
authors: Gerhard
authors: G
authors: Faller
authors: Institute of Pathology, Friedrich-Albert-University Freiburg, Germany.
authors: Martin
authors: M
authors: Werner
authors: Institute of Pathology, St. Vincentius Hospital Karlsruhe, Germany. Electronic address: arno.dimmler@vincentius-ka.de.
authors: Arno
authors: A
authors: Dimmler
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007636:Keratoacanthoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D009154:Mutation; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D018125:Receptors, Transforming Growth Factor beta; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: EGFR; Keratoacanthoma; Skin carcinogenesis; Squamous cell carcinoma; TGFbeta