title: p53 genetic abnormalities and P-glycoprotein expression in stump and primary gastric carcinomas.
abstract: OBJECTIVE
  Genetic abnormalities of the p53 gene may play a major role in the carcinogenesis of gastric stump carcinomas (GSC) and intestinal-type primary gastric carcinomas (IPGC). Also, they may modulate P-gp expression producing chemoresistance. The aim of this article is to analyze p53 genetic abnormalities and the influence of p53 gene status on P-gp expression in both types of carcinomas.
  
  
  METHODS
  Forty-two paraffin-embedded samples of gastric carcinomas corresponding to 17 GSC and 25 IPGC were studied. P53 genetic abnormalities in exon 5-9 were screened by direct sequencing of PCR products. P53 and P-glycoprotein (P-gp) were assessed by a standard streptavidin-biotin immunoperoxidase method. Anti-p53 DO7 and anti-P-gp C494 were used as primary antibodies.
  
  
  RESULTS
  Fourteen p53 mutations were found, 5 in GSC (29%) and 9 in IPGC (36%). Thirteen mutations were base-pair substitutions that produced a change in the amino acid sequence. Eight mutations were located at exon 7 (57%). P53 nuclear immunopositivity was observed in 12 GSC (71%) and 15 IPGC (60%). Only two carcinomas (1 IPGC and 1 GSC) harboring a p53 mutation did not show any p53 expression. All except one of the gastric carcinomas having a p53 mutation showed medium or high P-gp expression. However, there was no difference in P-gp expression between tumors with and without p53 mutation.
  
  
  CONCLUSIONS
  The p53 genetic alterations found in GSC and IPGC could originate from a similar pathogenetic pathway. No association was demonstrated between p53 gene status and P-gp expression, although most of the carcinomas harboring a p53 mutation showed medium or high P-gp expression.
authors.affiliation: Department of Pathology and Surgery, School of Medicine, Miguel Hernandez University, Elche, Spain. israel.oliver@umh.es
authors.forename: Israel
authors.initials: I
authors.lastname: Oliver
authors.forename: Javier
authors.initials: J
authors.lastname: Lacueva
authors.forename: Victor
authors.initials: V
authors.lastname: Barberá
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldés
authors.forename: Ana
authors.initials: A
authors.lastname: Teruel
authors.forename: David
authors.initials: D
authors.lastname: Costa
authors.forename: Justo
authors.initials: J
authors.lastname: Medrano
authors.forename: Teresa
authors.initials: T
authors.lastname: Pérez-Vázquez
authors.forename: Paz
authors.initials: P
authors.lastname: Quesada
authors.forename: José
authors.initials: J
authors.lastname: Ferragut
authors.forename: Rafael
authors.initials: R
authors.lastname: Calpena
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D001706:Biopsy; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D005091:Exons; D018530:Gastric Stump / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016159:Tumor Suppressor Protein p53