title: Immunohistochemical analysis of the mechanistic target of rapamycin and hypoxia signalling pathways in basal cell carcinoma and trichoepithelioma.
abstract: BACKGROUND
  Basal cell carcinoma (BCC) is the most common cancer in Caucasians. Trichoepithelioma (TE) is a benign neoplasm that strongly resembles BCC. Both are hair follicle (HF) tumours. HFs are hypoxic microenvironments, therefore we hypothesized that hypoxia-induced signalling pathways could be involved in BCC and TE as they are in other human malignancies. Hypoxia-inducible factor 1 (HIF1) and mechanistic/mammalian target of rapamycin (mTOR) are key players in these pathways.
  
  
  OBJECTIVE
  To determine whether HIF1/mTOR signalling is involved in BCC and TE.
  
  
  METHODS
  We used immunohistochemical staining of formalin-fixed paraffin-embedded BCC (n = 45) and TE (n = 35) samples to assess activity of HIF1, mTORC1 and their most important target genes. The percentage positive tumour cells was assessed manually in a semi-quantitative manner and categorized (0%, <30%, 30-80% and >80%).
  
  
  RESULTS
  Among 45 BCC and 35 TE examined, expression levels were respectively 81% and 57% (BNIP3), 73% and 75% (CAIX), 79% and 86% (GLUT1), 50% and 19% (HIF1α), 89% and 88% (pAKT), 55% and 61% (pS6), 15% and 25% (pMTOR), 44% and 63% (PHD2) and 44% and 49% (VEGF-A). CAIX, Glut1 and PHD2 expression levels were significantly higher in TE when only samples with at least 80% expression were included.
  
  
  CONCLUSIONS
  HIF and mTORC1 signalling seems active in both BCC and TE. There are no appreciable differences between the two with respect to pathway activity. At this moment immunohistochemical analyses of HIF, mTORC1 and their target genes does not provide a reliable diagnostic tool for the discrimination of BCC and TE.
authors.affiliation: Department of Dermatology, Maastricht University Medical Centre, Maastricht, the Netherlands; GROW, School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Tjinta
authors.initials: T
authors.lastname: Brinkhuizen
authors.affiliation: Department of Dermatology, Maastricht University Medical Centre, Maastricht, the Netherlands; GROW, School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Chantal A H
authors.initials: CA
authors.lastname: Weijzen
authors.affiliation: Department of Pathology, Maastricht University Medical Centre, Maastricht, the Netherlands; GROW, School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Eben
authors.affiliation: Department of Dermatology, Maastricht University Medical Centre, Maastricht, the Netherlands; GROW, School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Monique R
authors.initials: MR
authors.lastname: Thissen
authors.affiliation: Department of Pathology, VieCuri medical Centre, Venlo, the Netherlands.
authors.forename: Ariënne M
authors.initials: AM
authors.lastname: van Marion
authors.affiliation: Department of Pathology, Laurentius Hospital, Roermond, the Netherlands.
authors.forename: Björn G
authors.initials: BG
authors.lastname: Lohman
authors.affiliation: Department of Pathology, Maastricht University Medical Centre, Maastricht, the Netherlands; GROW, School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Véronique J L
authors.initials: VJ
authors.lastname: Winnepenninckx
authors.affiliation: Department of Epidemiology, Maastricht University Medical Centre, Maastricht, the Netherlands; GROW, School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Patty J
authors.initials: PJ
authors.lastname: Nelemans
authors.affiliation: Department of Dermatology, Maastricht University Medical Centre, Maastricht, the Netherlands; Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, the Netherlands; GROW, School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands; Institute of Medical Biology, Immunos, Singapore, Singapore.
authors.forename: Maurice A M
authors.initials: MA
authors.lastname: van Steensel
mesh_terms: D000368:Aged; D002280:Basal Cell Carcinoma / Q000378:metabolism* / Q000473:pathology*; D015687:Cell Hypoxia; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009386:Neoplastic Syndromes, Hereditary / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology*; D013194:Staining and Labeling; D018709:Statistics, Nonparametric; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D058570:TOR Serine-Threonine Kinases