Vol.6, No 1, 1999 pp. 103 - 106
UC 616.33; 616-006
OVER - EXPRESSION OF p53 PROTEIN IN GASTRIC
ADENOMAS
Vuka Katić1, Ivanka Stamenković1, Suzuko Moritani2,
Aleksandar Nagorni1, Ljubinka Veličković1
1Faculty of Medicine, University of Niš, Serbia, Yugoslavia
2Shiga University of Medical Science, Seta, Ohtsu, Japan
Summary: The p53 gene is a nuclear phosphoprotein that regulates
DNA replication, cell proliferation and cell death. Although the precise
mechanisms by which p53 acts as a tumor supressor gene are not known, accumulating
evidence suggests that normal wilde - type p53 acts as a "molecular policeman",
preventing propagation of genetically damaged cells. The accumulated wilde
- type p53 binds to DNA and causes cells to arrest in the G1 phase of the
cell cycle. With loss of normal p53 gene cells which are exposed to mutagenic
agents replicate the damged DNA and the mutations become fixed in the genome.
To prove a stepwise fashion of tumor progression at the molecular level,
we compared the results of immunohistochemical expression of p53 protein
in gastric adenomas with results of immunohistochemical expression of p53
protein in gastric adenocarcinomas.
p53 was not expressed in the normal gastric mucosa but it was expressed
in 7 of 10 adenomas with low grade of atypia and in all 6 adenomas with
high grade of atypia. Among gastric adenocarcinomas, p53 protein was expressed
in 15 of 16 adenocarcinomas. The incidence of p53 expression in gastric
adenocarcinomas increased with depth of invasion (without any correlation
with mentioned clinical factors) and with the grade of undifferentiation.
Our findings suggest that the p53 gene plays an important role in the
origin of human gastric tumors.
Key words: p53 expression, stomach adenoma, immunohistochemistry
EKSPRESIJA p53 PROTEINA U ŽELUDAČNIM ADENOMIMA
Kratak sadržaj: Nuklearni fosfoprotein, p53 gen, reguliše DNA
replikaciju, ćelijsku proliferaciju i ćelijsku smrt. Mada nisu poznati
mehanizmi pomoću kojih p53 deluje kao supresorni gen, dokazano je da normalni
"wilde - type" p53 deluje kao "molekularni policajac", sprečavajući propagaciju
genetski oštećenih ćelija. Akumulisani "wilde - type" p53 se vezuje za
DNA i izaziva mirovanje ćelija u G1 fazi ćelijskog ciklusa. Sa gubitkom
normalnog p53 gena, ćelije koje su izložene mutagenim agensima replikuju
oštećenu DNA, pa samim tim mutacije postaju fiksirane u genomu.
Da bi se dokazao stepeničasti način tumorske progresije na molekularnom
nivou, uporedili smo rezultate imunohistohemijske ekspresije p53 proteina
u adenomima želuca sa rezultatima imunohistohemijske ekspresije p53 proteina
u adenokarcinomima želuca. Nema ekspresije p53 proteina u normalnoj mukozi
želuca ali je ima u 7 od 10 adenoma sa nisko - stepenom atipijom i u svih
6 adenoma sa visoko - stepenom atipijom. U adenokarcinomima, p53 proteinska
ekspresija je nađena u 15 od 16 ispitivanih adenokarcinoma. Učestalost
p53 proteinske ekspresije je povećana sa dubinom invazije i sa stepenom
dediferencijacije, dok nikakve korelacije nije bilo sa istaknutim kliničkim
faktorima.
Naši nalazi sugerišu da supresorni p53 gen igra važnu ulogu u nastajanju
želudačnih tumora u ljudi.
Ključne reči: p53 ekspresija, želudačni adenom, imunohistohemija