p53 gene mutations in gastric adenomas

Tohdo, Hiroko; Yokozaki, Hiroshi; Haruma, Ken; Kajiyama, Goro; Tahara, Eiichi

doi:10.1007/bf02899260

Cited by 52 publications

(20 citation statements)

References 11 publications

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“…The reported frequencies of other genetic alterations observed in gastric adenoma/dysplasia have also varied widely. Mutation of the p53 gene or overexpression of p53 protein have been reported to occur in 0% to 30% (Craanen et al, 1995;Joypaul et al, 1993;Kyokane et al, 1998;Tohdo et al, 1993), MSI in 4% to 42% (Semba et al, 1996;Tamura et al, 1996b), and LOH in 11% to 87% (Kim et al, 2001;Tamura et al, 1996b) of cases of gastric adenoma/dysplasia.…”

Section: Discussionmentioning

confidence: 99%

Molecular and Cellular Phenotypic Profiles of Gastric Noninvasive Neoplasia

Jin

Tamura

Honda

et al. 2002

Laboratory Investigation

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SUMMARY:According to the Padova international classification, 52 gastric noninvasive neoplasias (NIN) were classified as follows: 20 low-grade NIN (L-NIN); 9 high-grade NIN including suspicion for carcinoma without invasion (H-NIN); and 23 high-grade NIN including carcinoma without invasion (Ca-NIN). The molecular and cellular phenotypic profiles were investigated and compared. The APC gene was mutated in seven (35%) L-NIN, two (22%) H-NIN, and two (9%) Ca-NIN tumors; APC mutations were significantly more frequent in L-NIN compared with Ca-NIN tumors (p Ͻ 0.05). Mutations of the p53 gene were found in five (22%) Ca-NIN tumors but were not observed in L-NIN or H-NIN tumors (p Ͻ 0.05). Loss of heterozygosity involving at least one chromosomal locus was detected in 14 (61%) Ca-NIN tumors but was not detected in L-NIN or H-NIN tumors. High-frequency microsatellite instability (MSI-H) was detected in one (5%) L-NIN tumor and in six (26%) Ca-NIN tumors. The frequencies of loss of heterozygosity and MSI-H were significantly higher in Ca-NIN than in L-NIN or H-NIN tumors (p Ͻ 0.05). Nuclear accumulation of p53 protein was detected in no L-NIN tumors, 1 (11%) H-NIN tumor, and 10 (44%) Ca-NIN tumors (p Ͻ 0.01). All tumors with loss of hMLH1 expression exhibited MSI-H (p Ͻ 0.01). Cellular phenotypic analysis revealed that seven (35%) L-NIN tumors and one (4%) Ca-NIN tumor had complete-type intestinal metaplastic phenotype and that one (5%) L-NIN tumor and one (4%) Ca-NIN tumor had a gastric foveolar epithelial phenotype, whereas the remaining tumors exhibited an ordinary phenotype. Thus, the complete-type intestinal metaplastic phenotype was more characteristic of L-NIN tumors than of H-NIN or Ca-NIN tumors (p Ͻ 0.01). In summary, the Padova international classification correlated with both the molecular and cellular phenotypic profiles. In practice, p53 and hMLH1 immunohistochemistry discriminated Ca-NIN from L-NIN and H-NIN tumors. (Lab Invest 2002, 82:1637-1645.

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Section: Discussionmentioning

confidence: 99%

Molecular and Cellular Phenotypic Profiles of Gastric Noninvasive Neoplasia

Jin

Tamura

Honda

et al. 2002

Laboratory Investigation

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“…Alterations have been found, in addition to microsatellite instability [30][31][32], in the p53 [29,[33][34][35][36]] APC [36,37] APC/mutated in colorectal cancer (MCC) [38] and deleted in colorectal cancer (DCC) [36] genes. There is no mutation of the Kras oncogene [36,39].…”

Section: Epithelial Polypsmentioning

confidence: 99%

Cellular and molecular pathology of gastric carcinoma and precursor lesions: A critical review

Ming

1998

Gastric Cancer

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Abstract:The cellular and molecular pathology of gastric cancer and its precursors are reviewed and discussed. Gastric carcinogenesis is a multistep phenomenon, beginning with precancerous conditions. Among these, adenoma is a direct precursor, because of the dysplastic nature of its cells. However, gastric adenoma is relatively rare. Chronic atrophic gastritis (CAG) is the most common precancerous condition, in which intestinal metaplasia often occurs. Carcinoma develops in CAG through stages of hyperplasia and dysplasia involving both metaplastic and non-metaplastic glands. Molecular alterations, including replication error and p53 and APC gene mutation and aneuploidy have been found in some of these conditions, confirming their role in carcinogenesis. Carcinomas of the stomach are heterogeneous in cellular composition. Both intestinal and gastric types of cells are found in all types of tumors, indicating the unique characteristics of gastric cancer. Many molecular lesions have been found in gastric carcinomas. Basic changes involve replication errors, telomerase activity, and aberrant CD44 transcripts. Many other changes often show differences in the frequency of their occurrence between the two major histological types of gastric carcinoma: well differentiated versus poorly differentiated, or intestinal type versus diffuse type. The timing and frequency of these changes in the stomach differ from the timing and frequency in colonic carcinogeneis. Pathological evaluation remains reliable and meaningful, in basic research as well as clinical management. To obtain correlation with molecular alterations, the need for detailed pathologic classification of gastric carcinoma is recognized, taking into account its biologic behavior and grades of cell differentiation.The cellular and molecular pathology of gastric cancer and its precursors are reviewed and discussed. Gastric carcinomas are unique in their heterogeneity in both cellular composition and molecular changes.

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“…p53 mutations detected in gastritis have been documented by Stemmermann et al (1994) and Kodama et al (1998), while studies by Zheng and YouYoung (1998), Shiao et al (1994) and Ochiai et al (1996) show p53 alterations only in intestinal metaplasia. Mutations of p53 in early gastric cancer have been found by Tohodo et al (1993) and Uchino et al (1993), while Romitti et al (1998), Brito et al (1994) and Joypaul et al (1993) claim that p53 mutations are late events in gastric cancer. However, p53 alterations in these studies have been detected using a variety of methods such as the polymerase chain reaction (PCR), PCR -single-strand conformation polymorphism, direct sequencing and immunohistochemistry.…”

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confidence: 99%

Detection of p53 mutations in precancerous gastric tissue

et al. 2003

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Intestinal-type gastric cancer is preceded by gastritis and intestinal metaplasia. There is uncertainty regarding the stage at which genetic alterations in the p53 gene occur. Reactive oxygen species (ROS) may participate in the production of mutations and the inactivation of p53 is due to infection by the bacterium Helicobacter pylori. We have investigated whether alterations of the p53 gene can be detected in gastritis and intestinal metaplasia using the restriction site mutation assay. We also assessed the potential contribution of ROS to p53 inactivation using electron spin resonance spectroscopy (ESR) and correlated with the presence of H. pylori. In all, 35% of the gastritis samples and 45% of the intestinal metaplasia samples were found to contain mutations in exons 5 -8 of the p53 gene. Electron spin resonance spectroscopy analysis showed a significant increase in free radical levels in gastritis samples compared with normal, intestinal metaplasia and cancer samples, suggesting that free radicals present in gastritis may contribute to p53 mutations. There was no significant difference in free radical levels between the H. pylori-positive and -negative groups. However, a small subpopulation of the H. pylori-negative patients had much higher levels of free radicals. This suggests a more prominent role for other factors in ROS production.

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p53 gene mutations in gastric adenomas

Cited by 52 publications

References 11 publications

Molecular and Cellular Phenotypic Profiles of Gastric Noninvasive Neoplasia

Molecular and Cellular Phenotypic Profiles of Gastric Noninvasive Neoplasia

Cellular and molecular pathology of gastric carcinoma and precursor lesions: A critical review

Detection of p53 mutations in precancerous gastric tissue

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