T. Gunther et al., Mdm2 gene amplification in gastric cancer correlation with expression of mdm2 protein and p53 alterations, MOD PATHOL, 13(6), 2000, pp. 621-626
Citations number
33
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Mdm2, localized on chromosome 12, is considered a negative regulator of p53
function and seems to play a role in the pathogenesis of a variety of tumo
rs, The mdm2 amplification in advanced-stage gastric carcinoma has not yet
been investigated,
Mdm2 amplification was determined in 43 gastric carcinomas, and the genetic
results were correlated with mdm2 protein expression, p53 alterations, and
clinicopathologic data. The tumors were classified according to Lauren: 20
intestinal-type tumors, 19 tumors of diffuse growth inclusive of a primary
small cell carcinoma, and 4 carcinomas with mixed differentiation. Staging
was based on the pTNM classification system. Mdm2 and p53 were demonstrate
d by immunohistology on formalin-fixed and paraffin-embedded tumor tissue.
The mdm2 oncogene was amplified by nonradioactive hybridization of tumor DN
A with an mdm2 cDNA probe. The Southern blots were evaluated densitometrica
lly. For p53 mutation screening, we analyzed the highly conservative region
s of the p53 gene (exons 4 to 8) with the use of the polymerase chain react
ion-single-strand conformation polymorphism technique. Polymerase chain rea
ction products with band shifting were directly sequenced.
Mdm2 amplification was demonstrated in 18 tumors (41.8%). The mdm2 gene was
amplified more frequently in carcinomas with a diffuse growth pattern, Gas
tric carcinomas of the intestinal type, however, showed a higher frequency
of p53 alterations. There was no statistical significance of the molecular
genetic and immunohistologic results of the mdm2/p53 status to staging as w
ell as to age and sex of the patients.
The mdm2/p53 pathway is a part of the carcinogenesis of gastric carcinoma O
nly approximately 20% of gastric carcinomas failed to show mdm2 and/or p53
alterations. The upregulation of the mdm2 oncogene and the accompanying ina
ctivation of the tumor suppressor gene 53 seem to play a role above all in
carcinomas of the diffuse type.