OVEREXPRESSION OF MUTANT P53 AND C-ERBB-2 PROTEINS AND MUTATIONS OF THE P15 AND P16 GENES IN HUMAN GASTRIC-CARCINOMA - WITH RESPECT TO HISTOLOGICAL SUBTYPES AND STAGES
Ms. Wu et al., OVEREXPRESSION OF MUTANT P53 AND C-ERBB-2 PROTEINS AND MUTATIONS OF THE P15 AND P16 GENES IN HUMAN GASTRIC-CARCINOMA - WITH RESPECT TO HISTOLOGICAL SUBTYPES AND STAGES, Journal of gastroenterology and hepatology, 13(3), 1998, pp. 305-310
Although the mechanism remains obscure, two histological subtypes of g
astric carcinoma (GC), the diffuse and intestinal types, differ drasti
cally in epidemiological, clinical, pathological and biological charac
teristics. We investigated whether the genetic alterations of several
oncogenes and tumour suppressor genes could be correlated with the two
histological subtypes. In 60 patients with GC, the overexpression of
mutant p53 and c-erbB-2 oncoproteins was studied using immunohistochem
ical stains. Mutations of the p15 and p16 tumour suppressor genes were
assessed by polymerase chain reaction, Southern blotting, and direct
DNA sequencing. Overexpression of c-erbB-2 and p53 was found in 21 (35
.0%) and 27 (45.0%) patients, respectively. Overexpression of the c-er
bB-2 oncoprotein was more common in the intestinal type (15/32, 46.9%)
and the advanced stage (19/45, 42.2%) than in the diffuse type (6/28,
21.4%) and the early stage (2/15, 13.3%) of GC (P<0.05). Similarly, p
53 overexpression was more frequently found in the intestinal type (19
/32, 59.4%) and the advanced st-age (24/45, 53.3%) than in the diffuse
type (8/28, 28.6%) and the early stage (3/15, 20.0%) of GC (P<0.05).
Homozygous deletions of p16 in exon 1 were found in six (10.0%) patien
ts. Five of them had the intestinal-type advanced GC. Neither point mu
tations of p16 nor alterations of p15 were detected. The frequency of
alterations of p53, c-erbB-2, and p16 was not related to sex and Helic
obacter pylori infection. No correlation of genetic changes between an
y two genes was observed. Our preliminary results indicate alterations
in the p15 gene were not important in gastric tumorigenesis, while in
frequent homozygous deletions in the p16 gene play a limited role in t
umour progression of intestinal-type GC. Moreover, overexpression of c
-erbB-2 and p53 is frequently encountered in the intestinal-type advan
ced GC. Alterations of p53, c-erbB-2: and p16 genes may function indep
endently of each other in gastric carcinogenesis. The association betw
een genetic alterations and histological subtypes supports the notion
that a distinct pathogenesis may exist in different histological subty
pes.