Chronology of p53 protein accumulation in gastric carcinogenesis.

Craanen, M. E.; Blok, P.; Dekker, W.; Offerhaus, G. Johan A.; Tytgat, G. N. J.

doi:10.1136/gut.36.6.848

Cited by 55 publications

(43 citation statements)

References 38 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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“…Selected results of some of the reports are included in Table 7. Overexpression and mutation of p53 were seen more frequently in the intestinal type than in diffuse type carcinomas [116,117] and more in the differentiated than the undifferentiated carcinomas [29,117,119,120]. The alterations occur early and remain at the same level in the intestinal type carcinomas [118].…”

Section: Molecular Alterations In Gastric Carcinomamentioning

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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“…Notably, mutations in APC, CTNNB1 (b-catenin) and/or p53 genes (Craanen et al, 1995;Park et al, 1999) are more frequently associated with the intestinal type, whereas aberrant expression of CDH1 (encoding E-cadherin) is often a feature of diffuse-type gastric cancers; somatic mutations of CDH1, or methylation in its promoter region, occur in about 50% of these tumors (Becker et al, 1994). Additionally, a limited number of genes including IQGAP1 (Takemoto et al, 2001), TGFb1, TGFbRII (Chung et al, 1997;Maehara et al, 1999), HGF and HGFR (c-met) , have been reported to show altered expression in diffuse-type gastric cancers.…”

Section: Introductionmentioning

confidence: 99%

Comparison of gene-expression profiles between diffuse- and intestinal-type gastric cancers using a genome-wide cDNA microarray

et al. 2004

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Gastric cancer is the fourth leading cause of cancerrelated death in the world. Two histologically distinct types of gastric carcinoma, 'intestinal' and 'diffuse', have different epidemiological and pathophysiological features that suggest different mechanisms of carcinogenesis. A number of studies have investigated intestinal-type gastric cancers at the molecular level, but little is known about mechanisms involved in the diffuse type, which has a more invasive phenotype and poorer prognosis. To clarify the mechanisms that underlie its development and/or progression, we compared the expression profiles of 20 lasermicrobeam-microdissected diffuse-type gastric-cancer tissues with corresponding noncancerous mucosae by means of a cDNA microarray containing 23 040 genes. We identified 153 genes that were commonly upregulated and more than 1500 that were commonly downregulated in the tumors. We also identified a number of genes related to tumor progression. Furthermore, comparison of the expression profiles of diffuse-type with those of intestinal-type gastric cancers identified 46 genes that may represent distinct molecular signatures of each histological type. The putative signature of diffuse-type cancer exhibited altered expression of genes related to cellmatrix interaction and extracellular-matrix (ECM) components, whereas that of intestinal-type cancer represented enhancement of cell growth. These data provide insight into different mechanisms underlying gastric carcinogenesis and may also serve as a starting point for identifying novel diagnostic markers and/or therapeutic targets for diffuse-type gastric cancers.

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Chronology of p53 protein accumulation in gastric carcinogenesis.

Abstract: Whenever intestinal metaplasia was present in the mucosa, 5 ,um sections were cut and stained with Alcian blue pH 2.5/periodic acid Schiff (AB pH 2-5/PAS) and high-irondiamine/Alcian blue for subtyping of intestinal

Cited by 55 publications

References 38 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

Comparison of gene-expression profiles between diffuse- and intestinal-type gastric cancers using a genome-wide cDNA microarray

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