title: Differential expression of p-mTOR in cutaneous basal and squamous cell carcinomas likely explains their different response to mTOR inhibitors in organ-transplant recipients.
abstract: BACKGROUND
  Mammalian Target of Rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have been shown to reduce cutaneous carcinogenesis in organ-transplant recipients requiring for immunosuppressive treatment to prevent from allograft rejection. Clinical observations suggest that cutaneous squamous cell carcinomas (SCC) are more sensitive than basal cell carcinomas (BCC) to the antitumoral effect of these inhibitors.
  
  
  OBJECTIVE
  To investigate if the different response of SCC and BCC to mTOR inhibitors can be explained by differential expression of molecules involved in the mTOR signaling pathway.
  
  
  METHODS
  The expression of phospho-mTOR was immunohistocemically studied in specimens of cutaneous SCC and BCC. Results. All 15 SCCs expressed significant cytoplasmic phospho-mTOR immunoreactivity; by contrast, 12/13 BCC were completely negative, only one BCC exhibited weak phospho-mTOR immunoreactivity.
  
  
  CONCLUSIONS
  The considerably higher expression of phospho-mTOR in SCC compared to BCC is a likely explanation for their higher sensitivity to mTOR inhibitors.
authors.affiliation: Department of Dermatology, Ed. Herriot Hospital (Pav. R), 69437 Lyon cx 03, France. jean.kanitakis@univ-lyon1.fr.
authors.forename: Georgia
authors.initials: G
authors.lastname: Karayannopoulou
authors.forename: Sylvie
authors.initials: S
authors.lastname: Euvrard
authors.forename: Jean
authors.initials: J
authors.lastname: Kanitakis
mesh_terms: D002280:Basal Cell Carcinoma / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016377:Organ Transplantation; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: basal cell carcinoma; everolimus; immunohistochemistry; immunosuppression; mTOR; organ transplantation; phospho-mTOR; sirolimus; skin; squamous cell carcinoma