Clonal Expansion and Loss of Heterozygosity at Chromosomes 9p and 17p in Premalignant Esophageal (Barrett's) Tissue

Galipeau, Patricia C.; Prevo, Laura J.; Sanchez, Carissa A.; Longton, Gary; Reid, Brian J.

doi:10.1093/jnci/91.24.2087

Cited by 182 publications

(127 citation statements)

References 50 publications

Supporting

Mentioning

116

Contrasting

Unclassified

Order By: Relevance

“…Barrett's esophagus is recognized as a phenotypically and genotypically heterogeneous structure formed by several distinct genetic clones. [23][24][25][26] This study identified different clones with distinct karyotypes in the same patient confirming this statement and illustrating the chromosomal instability present in Barrett's esophagus even in the absence of dysplasia or cancer. This instability may facilitate the expansion of clones carrying particular abnormalities with selective advantages as has been described for loss of heterozigosity at 17p and 9p.…”

Section: Discussionsupporting

confidence: 72%

“…This instability may facilitate the expansion of clones carrying particular abnormalities with selective advantages as has been described for loss of heterozigosity at 17p and 9p. [23][24][25][26] Conventional cytogenetics has, over other methods of chromosomal analysis, the ability to detect and characterize specific abnormalities. Its widespread routine application on Barrett's esophagus is not feasible mostly due to the difficulties in culturing nonneoplastic cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Chromosomal analysis of Barrett's cells: demonstration of instability and detection of the metaplastic lineage involved

et al. 2007

View full text Add to dashboard Cite

Barrett's esophagus is lined by columnar and goblets cells with gastric and intestinal characteristics. Despite the association between goblet elements and malignancy, it was not demonstrated that other columnar cells lineages are not related to neoplasia. Chromosomal abnormalities were described in metaplasia adjacent to Barrett's neoplasia, but it is unknown which metaplastic lineages are involved. This work assessed the frequency and the type of chromosomal abnormalities in Barrett's esophagus without neoplasia and performed the identification of the metaplastic cells carrying chromosomal gains. Barrett's esophagus biopsies were collected and processed for short-term cell culture and cytogenetic analysis. Combined immunofluorescence/ fluorescence in situ hybridization was performed in cases exhibiting chromosomal gains by using antisera against intestinal (MUC2) and gastric (MUC5AC and MUC6) apomucins and chromosome pericentromeric alpha satellite DNA probes for the chromosomes involved. Each case was scored for the number of spots (0, 1, 2, 42) in 200 nonoverlapping nuclei. Columnar and goblet cells were separately assessed. Short-term cell cultures were achieved in 40/60 cases (67%). There were clonal abnormalities in 27/40 cases (68%) and tetraploid (4n) clones in 10/40 (25%). Structural alterations were detected in 14/40 (35%) with recurrent breakpoints at 1q21, 15q15 and 15q22. Numerical changes (trisomies 7 and 18 and loss of Y) occurred in 16/40 (40%). Gains of chromosomes 7 and 18 were more frequent in columnar than in goblet cells (9.8% vs 0.7% (Po0.05)) and (7.9 vs 1.9% (Po0.05)) respectively. These alterations were detected in cells exhibiting gastric as well as intestinal features and were more frequent in cells without apomucin production. Conclusions: (1) chromosomal instability is a common finding in Barrett's esophagus without neoplasia. (2) The two metaplastic populations are committed, chromosomal gains being more frequent in columnar nongoblet than in goblet cells. (3) The two metaplastic phenotypes, gastric and intestinal, are equally involved.

show abstract

Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Chromosomal analysis of Barrett's cells: demonstration of instability and detection of the metaplastic lineage involved

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Although several studies have investigated the role of different oncogenes and tumor suppressor genes in esophageal carcinogenesis (Dolan et al, 1999;Jankowski et al, 1999;Roncalli et al, 1998;Walch et al, 2000;Wu et al, 1998), focusing on the advanced stages of progression from dysplasia to neoplasia, scarce data are available on genetic alterations occurring in Barrett's esophagus in the absence of neoplastic and/or dysplastic changes (Campomenosi et al, 1996;Galipeau et al, 1999 ). Three major histological forms of Barrett's esophagus have been described: a specialized columnar type, a cardiac type, and a fundic type.…”

mentioning

confidence: 99%

Molecular Alterations of Barrett's Esophagus on Microdissected Endoscopic Biopsies

Romagnoli

Roncalli

Graziani

et al. 2001

Laboratory Investigation

View full text Add to dashboard Cite

SUMMARY:Alterations in proto-oncogenes and tumor suppressor genes play a role in the sequence from Barrett's metaplasia to esophageal adenocarcinoma. The present study aims to ascertain whether molecular abnormalities take place in Barrett's metaplasia and low-grade dysplasia and to correlate them with the histological features of the esophageal mucosa. Forty-one formalin-fixed, paraffin-embedded endoscopic esophageal biopsies were classified according to the type of metaplastic changes (noncolumnar fundic and cardial metaplasia; columnar metaplasia, with and without intestinal features). After microdissection samples were examined for loss of heterozygosity (LOH) using polymorphic markers on 5q (D5S82), corresponding to APC (adenomatous polyposis coli) gene, 13q (CA repeat in intron 2 position 14815 to 14998 of the retinoblastoma gene), 17p (D17S513) corresponding to p53 locus, and for p53 mutations. Molecular alterations including LOH, allelic imbalance, and microsatellite instability could be detected in all types of metaplastic changes and sporadically in the squamous epithelium adjacent to the metaplastic tissue. Molecular alterations involving microsatellites D5S82 and the CA repeat inside the retinoblastoma gene were more frequent in nonintestinal metaplasia whereas those involving the p53 locus took place in columnar intestinal metaplasia and in low-grade dysplasia. Clonal changes were demonstrated in different metaplastic areas in three patients. Genetic alterations comprising LOH and microsatellite instability characterize Barrett's mucosa and appear related to the type of metaplastic change. Some of them precede the development of intestinal metaplasia, suggesting that genetic alterations take place earlier than previously thought. (Lab Invest 2001, 81:241-247).

show abstract

“…Loss of heterozygosity of chromosome 17p has been determined to be a marker of Barrett's esophagus progression. 5 A p53 mutation has been shown in the progression of Barrett's esophagus and is the underlying genetic change for loss of heterozygosity in chromosome 17p. 22 Tumor suppressor genes, such as p16, RUNX3, and HPP1 that undergo methylation, have been shown in one study 23 to function as biomarkers for predicting the progression of Barrett's esophagus to adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4] This variation is highest between low-grade dysplasia and indefinite for dysplasia and between high-grade dysplasia and early invasive adenocarcinoma. 3 Testing for aneuploidy, tetraploidy, and p16 and p53 genetic abnormalities, such as the loss of heterozygosity of chromosomes 9p and 17p, [5][6][7] have been shown to correlate with the risk of adenocarcinoma, but this is difficult to obtain in routine surgical pathology practice, particularly given the limited amount of tissue available in an endoscopic biopsy sample. Immunohistochemical markers, such as a-methyl coenzyme A racemase (AMACR), p53, caspase 3, and survivin, are promising as ancillary tests to facilitate the grading of dysplasia and to diagnose early adenocarcinoma in Barrett's esophagus.…”

mentioning

confidence: 99%

Anti-phosphorylated histone H3 expression in Barrett's esophagus, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma

Goodarzi

Correa

Ajani³

et al. 2009

Modern Pathology

View full text Add to dashboard Cite

The high interobserver variability in grading dysplasia in Barrett's esophagus demands a biomarker that can be applied in routine surgical pathology practice. Immunohistochemistry for phosphorylated histone H3 is a reliable marker of identifying mitotic figures and has not been evaluated in Barrett's esophagus-associated neoplastic lesions. We retrospectively studied the expression of phosphorylated histone H3 in 88 endoscopic biopsy samples of Barrett's esophagus without dysplasia (n ¼ 19), indefinite for dysplasia (n ¼ 11), low-grade dysplasia (n ¼ 27), high-grade dysplasia (n ¼ 19), or adenocarcinoma (n ¼ 12) from a sample of 54 patients. The samples were included after consensus diagnosis of two gastrointestinal pathologists on the hematoxylineosin (HE)-stained sections. Anti-phosphorylated histone H3-labeled mitotic figures were counted per 10 consecutive high-power fields (HPFs) in three distinct regions: surface epithelium, upper 2/3, and lower 1/3 of the crypts. Anti-phosphorylated histone H3-labeled mitotic counts for the three compartments of the crypts and the total scores for Barrett's esophagus, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma were compared using the Mann-Whitney U test. For each compartment, the number of anti-phosphorylated histone H3-positive nuclei was higher in low-grade dysplasia than in Barrett's esophagus without dysplasia or indefinite for dysplasia (Po0.001), but no difference was found between Barrett's esophagus without dysplasia and indefinite for dysplasia. High-grade dysplasia biopsies had significantly more anti-phosphorylated histone H3-labeled mitotic figures in the surface epithelium than the low-grade dysplasia (Po0.001). Adenocarcinoma had higher anti-phosphorylated histone H3-labeled mitotic figures than the highgrade dysplasia (Po0.001). Our data support the previous findings of expansion of the proliferative zone and importance of surface mitotic figure in the progression of Barrett's esophagus-low-grade dysplasia-highgrade dysplasia. In addition, phosphorylated histone H3 is a potential supportive marker to histology in differentiating low-grade dysplasia from indefinite for dysplasia and high-grade dysplasia from adenocarcinoma in the mucosal biopsy samples.

show abstract

Clonal Expansion and Loss of Heterozygosity at Chromosomes 9p and 17p in Premalignant Esophageal (Barrett's) Tissue

Cited by 182 publications

References 50 publications

Chromosomal analysis of Barrett's cells: demonstration of instability and detection of the metaplastic lineage involved

Chromosomal analysis of Barrett's cells: demonstration of instability and detection of the metaplastic lineage involved

Molecular Alterations of Barrett's Esophagus on Microdissected Endoscopic Biopsies

Anti-phosphorylated histone H3 expression in Barrett's esophagus, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma

Contact Info

Product

Resources

About