title: Impact of WWOX alterations on p73, ΔNp73, p53, cell proliferation and DNA ploidy in salivary gland neoplasms.
abstract: OBJECTIVE
  WWOX gene is altered in a variety of neoplasms. Wwox is pro-apoptotic through interaction with p73 and may be involved in chromosomal stability by interaction with p73 and p53. The aims of this study were to characterize WWOX transcription, methylation status and immunoexpression in salivary neoplasms and to determine whether these were associated with p73, p53, cell proliferation and DNA ploidy.
  
  
  METHODS
  Seven malignant and 21 benign fresh salivary neoplasms were included. WWOX expression was determined by RT-PCR and sequencing of transcripts, quantitative PCR and immunohistochemistry. Methylation-specific PCR was used to assess the methylation of its first exon. For p73, ΔNp73, p53 and ki67 immunohistochemistry and ploidy analysis, 29 malignant samples from archives were included.
  
  
  RESULTS
  No consistent pattern of WWOX exon 1 methylation was found, but aberrant and novel transcripts were observed in 17/28 neoplasms; 55% of tumours showed reduced WWOX RNA. WWOX RNA levels were associated with p53 immunopositivity. Immunohistochemical Wwox expression did not correlate with methylation status, p53 or p73 expression or proliferation. p73, proliferation and DNA ploidy were associated with malignant phenotype.
  
  
  CONCLUSIONS
  Aberrant WWOX transcription and decreased expression are frequent in salivary neoplasms and WWOX transcription is associated with p53 staining.
authors.affiliation: Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. carolinacavalieri@ufmg.br
authors.forename: C C
authors.initials: CC
authors.lastname: Gomes
authors.forename: M G
authors.initials: MG
authors.lastname: Diniz
authors.forename: C S
authors.initials: CS
authors.lastname: Oliveira
authors.forename: M
authors.initials: M
authors.lastname: Tavassoli
authors.forename: E W
authors.initials: EW
authors.lastname: Odell
authors.forename: R S
authors.initials: RS
authors.lastname: Gomez
authors.forename: L
authors.initials: L
authors.lastname: De Marco
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000782:Aneuploidy; D017209:Apoptosis / Q000235:genetics*; D049109:Cell Proliferation; D004247:DNA / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004171:Diploidy; D005091:Exons / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics*; D010641:Phenotype; D011003:Ploidies; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000074584:WW Domain-Containing Oxidoreductase; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C495901:TP53 protein, human; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human; D004247:DNA; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human