Genetic differences between adenocarcinomas arising in Barrett's esophagus and gastric mucosa

El–Rifai, Wael; Frierson, Henry F.; Moskaluk, Christopher A.; Harper, Jeffrey C.; Petroni, Gina R.; Bissonette, Eric A.; Jones, David R.; Knuutila, Sakari; Powell, Steven M.

doi:10.1053/gast.2001.27215

Cited by 73 publications

(41 citation statements)

References 22 publications

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“…This observation is also interesting because human CLDN7 is located at chromosome 17 (17p13), which has frequent alterations in DNA copy numbers in gastric cancer. 17,18 Our studies demonstrate that CLDN7 up-regulation in gastric neoplasia is conserved between the mouse model and human disease. Using clinical samples, Cldn7 IHC staining was not detected in any normal tissues, whereas specific cytoplasmic staining with apical patterns was seen in intestinal metaplasia, dysplasia, and adenocarcinomas.…”

Section: Discussionmentioning

confidence: 74%

Expression of Tight-Junction Protein Claudin-7 Is an Early Event in Gastric Tumorigenesis

Johnson

Frierson

Zaika

et al. 2005

The American Journal of Pathology

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Trefoil factor-1 (Tff1) expression is remarkably downregulated in nearly all human gastric cancers. Therefore, we used the Tff1 knockout mouse model to detect molecular changes in preneoplastic gastric dysplasia. Oligonucleotide microarray gene expression analysis of gastric dysplasia of Tff1 ؊/؊ mice was compared to that of normal gastric mucosa of wild-type mice. The genes most overexpressed in Tff1؊/؊ mice included claudin-7 (CLDN7), early growth response-1 (EGR1), and epithelial membrane protein-1 (EMP1). Quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry showed that Cldn7 was overexpressed in all 10 Tff1؊/؊ gastric dysplasia samples. Comparison with our serial analysis of gene expression database of human gastric cancer revealed similar deregulation in human gastric cancers. Quantitative real-time reverse transcriptase-polymerase chain reaction of human gastric adenocarcinoma samples indicated that, of these three genes, CLDN7 was the most frequently up-regulated gene. Using immunohistochemistry, both mouse and human gastric glands overexpressed Cldn7 in dysplastic but not surrounding normal glands. Cldn7 expression was observed in 30% of metaplasia, 80% of dysplasia, and 70% of gastric adenocarcinomas. Interestingly, 82% of human intestinal-type gastric adenocarcinomas expressed Cldn7 whereas diffuse-type gastric adenocarcinomas did not (P < 0.001). These results suggest that Cldn7 expression is an early event in gastric tumorigenesis that is maintained throughout tumor progression. Gastric carcinoma is the second leading cause of cancer mortality worldwide accounting for ϳ10% of newly diagnosed cancers.

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Section: Discussionmentioning

confidence: 74%

Expression of Tight-Junction Protein Claudin-7 Is an Early Event in Gastric Tumorigenesis

Johnson

Frierson

Zaika

et al. 2005

The American Journal of Pathology

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101

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“…26,27 A variety of gains and losses of specific chromosomes and chromosome regions have also been detected in esophageal adenocarcinoma specimens and adjacent mucosa by both traditional cytogenetics and by comparative genomic hybridization. [34][35][36][37][38][39] The studies consistently show an accumulation of chromosomal abnormalities as the histologic changes progress from intestinal metaplasia to dysplasia and carcinoma. 4,[40][41][42][43] Previously reported changes detectable by FISH in esophagectomy specimens suggested that gains of chromosomes 6, 7, 11, and 12 might be among the numerical abnormalities occurring most frequently in the Barrett's esophagus-associated HGD and adenocarcinoma, findings which we have confirmed with the use of endoscopic cytology specimens.…”

Section: Discussionmentioning

confidence: 99%

Chromosomal gains and genomic loss of p53 and p16 genes in Barrett's esophagus detected by fluorescence in situ hybridization of cytology specimens

et al. 2004

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Endoscopic brush cytology is a promising surveillance technique for Barrett's esophagus. Ancillary markers are sought to increase the sensitivity of cytology and allow identification of patients at increased risk for disease progression. To determine if there are specific genetic changes in Barrett's esophagus with associated high-grade dysplasia/intramucosal adenocarcinoma compared to those without dysplasia, we performed fluorescence in situ hybridization (FISH) on cytologic specimens using probes to chromosomes and genomic regions previously described as altered in this disease. We studied archival brush cytology slides from 40 Barrett's esophagus patients: 21 with biopsy-proven high-grade dysplasia/carcinoma and 19 with no dysplasia and a minimum 5 years of negative follow-up. Centromeric enumeration probes (CEP) for chromosomes 6, 7, 11, and 12, and locus-specific probes (LSI) for 9p21 (p16 gene), and 17p13.1 (p53 gene) loci along with their corresponding CEP (9 and 17, respectively) were used in this study. A positive FISH result was defined as the presence of cells with 42 CEP signals or with a loss of the LSI signals relative to their corresponding CEP. p53 locus loss and/or aneusomy of chromosomes 6, 7, 11, and 12 abnormalities could be detected by FISH in routinely processed endoscopic brush cytology specimens from 95% of biopsy-positive cases with a specificity of 100%. Interestingly, all five cases with cytologic changes classified as indefinite for dysplasia from patients with a positive biopsy showed changes by FISH. Loss of the p16 locus was seen commonly in patients both with and without dysplasia/carcinoma. Selected biomarkers from this study merit further investigation to determine their potential to detect genetic changes in patients with Barrett's esophagus prior to the development of high-grade dysplasia.

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“…We have previously reported that early-stage of C-Ca is associated with higher frequency of gastric phenotypic marker expression and lower frequency of intestinal metaplasia of the surrounding mucosa as compared with early-stage of D-Ca (Tajima et al, 2001a). Recent investigations have also shown that genetic aberrations in the C-Ca gene are probably more closely associated with O-Ca than with D-Ca (El-Rifai et al, 2001;Stocks et al, 2001). These differences in characteristics between C-Ca and D-Ca suggest that C-Ca might represent a distinct subtype of gastric carcinoma.…”

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confidence: 96%

Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach

et al. 2007

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Adenocarcinoma of the gastric cardia (C-Ca) is possibly a specific subtype of gastric carcinoma. The purpose of this study was to clarify the differences in the clinicopathological characteristics between C-Ca and adenocarcinoma of the distal stomach (D-Ca), and also the differences in the expressions of gastric and intestinal phenotypic markers and genetic alterations between the two. The clinicopathological findings in 72 cases with C-Ca were examined and compared with those in 170 cases with D-Ca. The phenotypic marker expressions examined were those of human gastric mucin (HGM), MUC6, MUC2 and CD10. Furthermore, the presence of mutations in the APC, K-ras and p53 genes and the microsatellite instability status of the tumour were also determined. C-Ca was associated with a significantly higher incidence of differentiated-type tumours and lymphatic vessel invasion (LVI) as compared with D-Ca (72.2 vs 48.2%, P ¼ 0.0006 and 72.2 vs 55.3%, P ¼ 0.0232, respectively). Oesophageal invasion by the tumour beyond the oesophago-gastric junction (OGJ) was found in 56.9% of cases with C-Ca; LVI in the area of oesophageal invasion was demonstrated in 61% of these cases. Also, LVI was found more frequently in cases of C-Ca with oesophageal invasion than in those without oesophageal invasion (82.9 vs 58.1%, P ¼ 0.0197). The incidence of undifferentiated-type tumours was significantly higher in cases with advanced-stage C-Ca than in those with early-stage C-Ca (5 vs 36.5%, P ¼ 0.0076). A significantly greater frequency of HGM expression in early-stage C-Ca and significantly lower frequency of MUC2 expression in advanced-stage C-Ca was observed as compared with the corresponding values in cases of D-Ca (78.9 vs 52.2%, P ¼ 0.0402 and 51.5 vs 84.6%, P ¼ 0.0247, respectively). Mutation of the APC gene was found in only one of all cases of C-Ca, and the frequency of mutation of the APC gene was significantly lower in cases of C-Ca than in those of D-Ca (2.4 vs 20.0%, P ¼ 0.0108). The observations in this study suggest that C-Ca is a more aggressive tumour than D-Ca. The differences in biological behavior between C-Ca and D-Ca may result from the different histological findings in the wall of the OGJ and the different genetic pathways involved in the carcinogenesis.

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Genetic differences between adenocarcinomas arising in Barrett's esophagus and gastric mucosa

Cited by 73 publications

References 22 publications

Expression of Tight-Junction Protein Claudin-7 Is an Early Event in Gastric Tumorigenesis

Expression of Tight-Junction Protein Claudin-7 Is an Early Event in Gastric Tumorigenesis

Chromosomal gains and genomic loss of p53 and p16 genes in Barrett's esophagus detected by fluorescence in situ hybridization of cytology specimens

Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach

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