p53 genetic abnormalities and P-glycoprotein expression in stump and primary gastric carcinomas.
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.
Oliver
Israel
I
Department of Pathology and Surgery, School of Medicine, Miguel Hernandez University, Elche, Spain. israel.oliver@umh.es
Lacueva
Javier
J
Barberá
Victor
V
Caldés
Trinidad
T
Teruel
Ana
A
Costa
David
D
Medrano
Justo
J
Pérez-Vázquez
Teresa
T
Quesada
Paz
P
Ferragut
José
J
Calpena
Rafael
R
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*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016159:Tumor Suppressor Protein p53