Gastric adenocarcinoma and Helicobacter pylori: Correlation with p53 mutation and p27 immunoexpression
ABSTRACT 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.
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.
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.
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.
- SourceAvailable from: Ahmad Daneshi
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- "Helicobacter pylori (HP) is one of the risk factors of adenocarcinoma. Thus, it was categorized as a carcinogen in 1994 by the World Health Organization (WHO) [1,2]. Recent studies have revealed that HP can be responsible for the pathogenesis of upper gastro-esophageal tract lesions such as oral cavity. "
ABSTRACT: Although Helicobacter Pylori (HP) was detected in some cases of chronic laryngitis, the results were not confirmed by polymerase chain reaction (PCR). By this time, it has not been found in laryngeal lesions by in house PCR, the most sensitive method for detecting the genome tracks. Regarding the previous results and also few numbers of studies about the presence of HP in benign laryngeal lesions, specifically by PCR, we aimed to investigate the presence of HP in benign laryngeal lesions by in-house PCR. The samples were taken from 55 patients with benign laryngeal lesions and frozen in -20°C. One milliliter (ml) of lysis buffer was added to 100 mg (mg) of each sample and the tube was placed in 56°C overnight. Then DNA extraction was carried out. To find HP DNA, in-house PCR was performed that revealed 5 positive results among 55 patients with benign laryngeal lesions. Of them, 3 were polyp, 1 was nodule and 1 was papilloma. Although the number of positive results was not a lot in this study, it was in contrast with previous studies which could not find any HP tracks in benign laryngeal lesions by other methods. More studies about the prevalence of HP in benign laryngeal lesions improve judging about the effect of this infection on benign laryngeal lesions.Infectious Agents and Cancer 04/2012; 7(1):10. DOI:10.1186/1750-9378-7-10 · 2.07 Impact Factor
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ABSTRACT: Floating gastric adenocarcinoma cells in ascitic fluid are the main cause of peritoneal dissemination. Activation of apoptosis is an important mechanism by which tumor cells are eliminated by the immune surveillance system. Hence, we examined caspase-9 expression and the apoptosis in gastric adenocarcinoma cells in ascitic fluid using immunohistochemistry, real-time polymerase chain reaction and in situ cell death detection kits, flow cytometry. The results revealed strong expression of caspase-9 in 58.49% (31/53) malignant cells and a relatively weak expression of caspase-9 in 41.51% (22/53) malignant cells. The proportion of apoptotic cells in 31 malignant cases with strong caspase-9 expression (35.14 ± 3.42)% was significantly higher than that in 22 malignant cases with relatively weak caspase-9 expression (17.29 ± 7.62)% or in mesothelial cells (10.76 ± 4.21%; p < 0.05). Kaplan-Meier survival curves demonstrated that the patients with low caspase-9 expression showed significantly shorter survival (p < 0.05) than those with high caspase-9 expression. These findings suggest that immune clearance gastric carcinoma cells in ascites activated by caspase-9 helped to improve the prognosis of patients with gastric cancer.Apmis 03/2011; 119(3):173-9. DOI:10.1111/j.1600-0463.2010.02707.x · 1.92 Impact Factor
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ABSTRACT: Evidence suggests that the carcinogenic process guided by Helicobacter pylori is related to the expression of cell cycle and apoptosis proteins as BCL-2, BAX, and MYC. However, the literature is conflicting regarding the expression frequency in the histological subtypes and did not consider cagA gene presence. To investigate the expression of these proteins considering the histological subtypes of gastric cancer associated with H. pylori (cagA), a total of 89 cases were used. H. pylori infection and cagA status were determined by PCR. Immunodetection was performed for MYC, BCL-2, and BAX proteins. H. pylori was found in 95.5% of the patients, among them, 65.8% were cagA(+). Nuclear MYC was detected in 36.4%, BAX in 55.7%, while BCl-2 in just 5%. Nuclear MYC staining was significantly lower in the intestinal than diffuse subtype (p = 0.008) and was related with the presence of H. pylori cagA(+). Additionally, most of the few cases cytoplasmic MYC positive were in the intestinal subtype. In diffuse tumors, although most nuclear MYC positive cases were cagA(+), it was not significant. No difference was observed between BCL-2 or BAX expression considering the presence of cagA gene in the histological subtypes. It seems that MYC could be relevant for the diffuse tumorigenic pathway associated with H. pylori and possibly influenced by the presence of cagA gene, while in intestinal tumors, the tumorigenic pathway does not occur through the MYC expression.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 06/2011; 458(6):725-31. DOI:10.1007/s00428-011-1085-y · 2.56 Impact Factor