title: Characterisation of the cutaneous pathology in non-small cell lung cancer (NSCLC) patients treated with the EGFR tyrosine kinase inhibitor erlotinib.
abstract: BACKGROUND
  EGFR inhibitors (EGFRIs) have been shown to be clinically effective in various cancers. Unique skin toxicity is commonly observed with EGFRIs and a correlation between the clinical benefit of EGFRIs and this characteristic rash has been reported. Erlotinib is a potent EGFRI approved for treatment of non-small cell lung cancer (NSCLC) and pancreatic cancer.
  
  
  METHODS
  This is the first time in which patients were given increasing doses of an EGFRI to induce a mechanistic rash and study its associated pathology in skin. Biopsies were collected during treatment from both rash-affected and unaffected skin of 23 NSCLC patients and compared with pre-treatment biopsies.
  
  
  RESULTS
  Altered differentiation of appendegeal epithelium (hair follicles and sebaceous glands) was remarkable in both affected and unaffected skin, although epidermal growth was not significantly reduced. A predominantly mononuclear leucocyte infiltrate was detected in the interfollicular dermis or around skin appendages. This infiltrate included TRAIL-positive cells with a dendritic cell (DC) morphology, although T-cells, antigen-presenting DCs and macrophages were also evident. This is the first report showing the involvement of a dendritic cell subtype with EGFRI skin toxicity.
  
  
  CONCLUSIONS
  Altered differentiation of pilosebaceous epithelium is evident in both rash-affected and unaffected skin and constitutes the primary process of EGFRI in human skin. We propose that this eventually triggers inflammation and the EGFRI rash. TRAIL-positive inflammatory cells could link rash development and immune-triggered apoptosis of epithelial cells, including those of underlying carcinomas.
authors.affiliation: The Laboratory for Investigative Dermatology, The Rockefeller University, NY 10065, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
authors.forename: Alain
authors.initials: A
authors.lastname: Mita
authors.forename: Maja
authors.initials: M
authors.lastname: De Jonge
authors.forename: Lesley
authors.initials: L
authors.lastname: Matthews
authors.forename: Sean
authors.initials: S
authors.lastname: McCarthy
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Iwata
authors.forename: Jaap
authors.initials: J
authors.lastname: Verweij
authors.forename: Eric K
authors.initials: EK
authors.lastname: Rowinsky
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D017209:Apoptosis; D001707:Biopsy, Needle; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003712:Dendrites / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D003875:Drug Eruptions / Q000209:etiology / Q000473:pathology*; D000069347:Erlotinib Hydrochloride; D005076:Exanthema / Q000139:chemically induced / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects*; D012867:Skin / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride