Gastric adenocarcinoma and Helicobacter pylori: correlation with p53 mutation and p27 immunoexpression.
BACKGROUND
Helicobacter pylori infection is an established risk factor for gastric cancer development, but the exact underlying mechanism still remains obscure. The inactivation of tumor suppressor genes such as p53 and p27(KIP1) is a hypothesized mechanism, although there is no consensus regarding the influence of H. pylori cagA(+) in the development of these genetic alterations.


OBJECTIVE
To verify the relationship among H. pylori infection, p53 mutations and p27(Kip1) Protein (p27) expression in gastric adenocarcinomas (GA) seventy-four tissues were assayed by PCR for H. pylori and cagA presence. Mutational analysis of p53 gene was performed by single-strand conformation polymorphism (SSCP). Seventy tissues were analyzed by an immunohistochemical method for p27 expression.


RESULTS
From the samples examined, 95% (70/74) were H. pylori positive, 63% cagA(+). Altered p53 electrophoretic mobility was found in 72% of cases and significantly more frequent in the presence of cagA. Considerable reduction in p27 expression (19%) was found with a tendency for association between cagA(+) and p27(-), although the results were not statistically significant. Concomitant alterations of both suppressor genes were detected in 60% of cases. In the cases cagA(+), 66.7% of them had these concomitant alterations.


CONCLUSIONS
The data suggest that H. pylori cagA(+) contributes to p53 alteration and indicate that concomitant gene inactivation, with reduced p27 expression, may be a mechanism in which H. pylori can promote the development and progression of gastric cancer.
André
Angela Rosa
AR
Molecular Genetics Laboratory, Department of Pathology and Forensic Medicine, Federal University of Ceará, Rua Alexandre Baraúna, 949, Rodolfo Téofilo, CEP 60430-160, Fortaleza-CE, Brazil. angelarandre@yahoo.com.br
Ferreira
Márcia Valéria Pitombeira
MV
Mota
Rosa Maria Salani
RM
Ferrasi
Adriana Camargo
AC
Pardini
Maria Inês de Moura Campos
MI
Rabenhorst
Sílvia Helena Barem
SH
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D020868:Gene Silencing; D016158:Genes, p53; D016481:Helicobacter Infections / Q000235:genetics* / Q000378:metabolism; D016480:Helicobacter pylori / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D055815:Young Adult
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; C080866:cagA protein, Helicobacter pylori; D050760:Cyclin-Dependent Kinase Inhibitor p27