Study of p53 immunostaining in the gastric epithelium of cagA-positive and cagA-negative Helicobacter pylori gastritis.
BACKGROUND
p53 mutations are an early event in the multistep progression of gastric carcinoma. These mutations are often present in dysplastic and intestinal metaplastic gastric epithelium. However, the presence of immunohistochemically detectable p53 protein and p53 mutations in nondysplastic/nonmetaplastic gastric mucosa is more controversial. Recent reports have suggested that immunohistochemically detectable p53 protein may be present in the gastric epithelium of Helicobacter pylori gastritis. Furthermore, because cagA-positive H. pylori is associated with greater mucosal injury but decreased apoptosis, it would be interesting to determine if this phenotype is associated with greater immunostaining of p53, as the wild-type p53 gene helps to initiate apoptosis.


METHODS
One hundred thirty-five patients with H. pylori-associated gastritis were immunohistochemically stained for p53 and quantified for the extent and intensity of the staining using a semiquantitative method (0, nil staining; 6, extensive and strong staining). The cagA status of the organism was determined by Western blot.


RESULTS
Thirty-one patients (23%) showed strong p53 staining (> or = 4 of 6) in inflamed but otherwise normal gastric epithelium. In the 123 cagA-positive H. pylori gastritis patients, the average p53 staining score was 2.5 of 6. This is significantly higher than the corresponding score of 1.7 of 6 observed in the 12 patients with cagA-negative H. pylori gastritis (P = 0.04).


CONCLUSIONS
Our results indicate that p53 protein is immunohistochemically detectable even before gastric metaplastic/dysplastic change occurs. The results also suggest that cagA-positive H. pylori might be associated with greater p53 immunohistochemical staining. This would indicate that p53 immunohistochemical staining does not reliably differentiate between gastric dysplasia and reactive inflammatory atypia. If the p53 protein detected is a consequence of mutation, this would help to explain why cagA-positive H. pylori gastritis is associated with decreased apoptosis.
Teh
Ming
M
Department of Pathology, National University of Singapore, National University Hospital, Lower Kent Ridge Road, Singapore 119074. pattehm@nus.edu.sg
Tan
Kong Bing
KB
Seet
Bee Leng
BL
Yeoh
Khay Guan
KG
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000032:analysis; D001426:Bacterial Proteins / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D005753:Gastric Mucosa / Q000737:chemistry / Q000473:pathology*; D005757:Gastritis, Atrophic / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D016481:Helicobacter Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori / Q000254:growth & development / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007422:Intestines / Q000737:chemistry / Q000473:pathology; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016159:Tumor Suppressor Protein p53; C080866:cagA protein, Helicobacter pylori