title: Does a low frequency of P53 and Pgp expression in familial glioma compared to sporadic controls indicate biological differences?
abstract: BACKGROUND
  A three-fold increased risk for glioma among first degree relatives (FDR) to glioma patients has previously been shown. This study compared familial cases with sporadic controls of glioma to see if phenotypic differences could be detected. Different pathways to tumour growth and progression were investigated including cell cycle regulating genes (p53) and growth factors (epidermal growth factor receptor, EGFR), angiogenesis (vascular endothelial growth factor, VEGF and microvessel density, MVD), pathways of detoxification (glutathione-S-transferase, GST pi) and multidrug resistance (P-glycoprotein, Pgp).
  
  
  METHODS
  Thirty-seven cases of familial gliomas, identified in a population-based study, were compared to 58 sporadic glioma controls chosen with a negative family history of glioma. The immunohistochemistry was performed with standard procedures using the LABSA kit (Zymed lab).
  
  
  RESULTS
  Familial cases had significantly more frequent p53- and Pgp-negative tumours, also when correcting for age, sex and histopathology. However, Pgp was no longer significant after correcting for p53 status indicating a correlation between Pgp and p53. A significant difference between VEGF-negative to VEGF-positive tumours (low- or high-grade) was shown, but it was no longer significant when correcting for p53 status.
  
  
  CONCLUSIONS
  Our study investigated phenotypic differences of familial glioma compared to sporadic control. Our finding of a distinct pattern of increased p53- and Pgp-negativity among cases warrants further investigation.
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, 90187 Umeå, Sweden. beatrice.malmer@onkologi.umu.se
authors.forename: Beatrice
authors.initials: B
authors.lastname: Malmer
authors.forename: Thomas
authors.initials: T
authors.lastname: Brännström
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bergh
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D005260:Female; D005910:Glioma / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D008222:Lymphokines / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008222:Lymphokines; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase