title: No evidence for human papillomavirus infection in focal cortical dysplasia IIb.
abstract: OBJECTIVE
  The etiology of focal cortical dysplasia type IIb (FCDIIb) remains enigmatic in patients suffering from drug-resistant epilepsy, and an aberrant activation of the mammalian target of rapamycin complex 1 signaling pathway (mTORC1) was detected in this developmental brain malformation. Recently, the human papillomavirus (HPV) oncoprotein E6 has been identified as a potent activator of mTORC1, and HPV16 E6 has been described to persist in balloon cells obtained from surgical FCDIIb specimens. Although this observation was replicated by an independent second report, it contradicts current knowledge of HPV biology. HPV infects the squamous or mucocutaneous epithelium; hematogenic spread into other tissues has not been observed. In addition, brain carcinogenesis has never been reported in FCDIIb patients. Herein, we have tried to confirm 2 previous reports of HPV16 E6 infection using an independent series of 14 surgical specimens with histopathologically confirmed FCDIIb.
  
  
  METHODS
  Snap-frozen FCDIIb specimens were tested for HPV DNA using the primer set for amplification of the complete E6 reading frame of HPV16 and 3 other sets of primers (2 consensus primer sets detecting multiple HPV genotypes, and another primer set specifically used for HPV16). Furthermore, formalin-fixed and paraffin-embedded histopathological preparations were immunohistochemically analyzed using previously described antibodies directed against the HPV E6 oncoprotein.
  
  
  RESULTS
  All 14 FCDIIb specimens were negative for HPV DNA with all 4 primer sets. Antibodies directed against the HPV E6 epitope showed weak labeling of cytoplasm in balloon cells, as previously described in FCDIIb, but also in other cell populations.
  
  
  CONCLUSIONS
  Our data did not confirm previously reported evidence for HPV16 detection in FCDIIb.
authors.affiliation: Department of Neuropathology, University Hospital Erlangen, Erlangen.
authors.forename: Roland
authors.initials: R
authors.lastname: Coras
authors.forename: Klaus
authors.initials: K
authors.lastname: Korn
authors.forename: Christian G
authors.initials: CG
authors.lastname: Bien
authors.forename: Thilo
authors.initials: T
authors.lastname: Kalbhenn
authors.forename: Karl
authors.initials: K
authors.lastname: Rössler
authors.forename: Katja
authors.initials: K
authors.lastname: Kobow
authors.forename: Johannes
authors.initials: J
authors.lastname: Giedl
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fleckenstein
authors.forename: Ingmar
authors.initials: I
authors.lastname: Blumcke
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000302:isolation & purification*; D005260:Female; D006801:Humans; D008297:Male; D054220:Malformations of Cortical Development / Q000175:diagnosis* / Q000601:surgery / Q000821:virology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000302:isolation & purification; D009856:Oncogene Proteins, Viral / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000453:epidemiology; D058570:TOR Serine-Threonine Kinases / Q000302:isolation & purification; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D046912:Multiprotein Complexes; D009856:Oncogene Proteins, Viral; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases