Oesophageal cancer incidence and mortality in patients with long-segment Barrett's Oesophagus after a mean follow-up of 12.7 years

Hage, Maria Cristina Ferrarini Nunes Soares; Siersema, Peter D.; Dekken, Herman van; Steyerberg, Ewout W.; Dees, Jan; Kuipers, Ernst J.

doi:10.1080/00365520410003524

Cited by 97 publications

(83 citation statements)

References 14 publications

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“…LOH was discriminated for all BE specimens combined at t 5 2 of 5q in 0%, 9p in 56%, 17p in 44% and 18q in 20% of informative cases. The LOH patterns of the BE's at t 5 0 (14 MET, 4 LGD, 3 HGD), t 5 1 (18 MET, 3 LGD) and t 5 2 (8 MET, 2 LGD) were not statistically different (Fig. 2b), despite histologic downgrading of dysplasia after therapy.…”

Section: Resultsmentioning

confidence: 93%

“…36 Although the latter is clear for patients with HGD, patients with MET and LGD also appear to have an increased risk. 4 We investigated 80 samples of BE before and after ablation by ALA-PDT or APC for LOH at tumor suppressor loci known to be involved in malignant progression in BE, i.e., the APC gene on 5q, P16 on 9p, the P53 gene on 17p and DCC and SMAD4 on 18q. Before treatment, frequency patterns of loss were observed that were in agreement with previously published reports, e.g., frequent LOH at the P16 locus starting already in metaplasia without dysplasia.…”

Section: Discussionmentioning

confidence: 99%

“…This metaplastic change is most likely the result of severe and longstanding esophageal reflux and carries an increased risk of developing esophageal adenocarcinoma. [1][2][3][4] Esophageal adenocarcinoma is preceded by premalignant epithelial changes, i.e., low-grade dysplasia (LGD) and high-grade dysplasia (HGD), the latter being synonymous to adenocarcinoma in situ. [5][6][7] Most commonly used ablative therapies are argon plasma coagulation and photodynamic therapy.…”

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confidence: 99%

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Genomic analysis of Barrett's esophagus after ablative therapy: Persistence of genetic alterations at tumor suppressor loci

Hage

Siersema

Vissers

et al. 2005

Intl Journal of Cancer

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Barrett's esophagus (BE) is a major predisposing factor for the development of esophageal adenocarcinoma. Current strategies for treatment of BE, both dysplastic and nondysplastic, include photodynamic therapy (PDT) and argon plasma coagulation (APC). However, the effect of ablative therapy at the genetic level is unclear. We performed loss of heterozygosity (LOH) analysis of BE in baseline and follow-up biopsy specimens from 21 patients with BE (17 male, 4 female) treated with PDT and/or APC. At baseline, 14 patients had intestinal metaplasia without dysplasia (MET), 4 low-grade dysplasia (LGD) and 3 high-grade dysplasia (HGD). LOH was assessed using a panel of 9 polymorphic markers for evaluation of the P53 gene on 17p, P16 on 9p, DCC and SMAD4 on 18q and the APC gene on 5q. The tissue specimens obtained at baseline (t 5 0) were analysed, as well as the first (t 5 1; mean interval: 4 months) and last (t 5 2; mean interval: 8 months) available biopsy with residual or recurrent BE after ablation. At t 5 0, allelic loss was detected of 5q in 27%, 9p in 56%, 17p in 31% and 18q in 6% of informative cases. At t 5 1 (18 patients with persistent MET and 3 with LGD) and at t 5 2 (8 MET, 2 LGD), the LOH patterns were not statistically different from t 5 0. Further, multiple genetic lineages before and after therapy were detected in 15 cases illustrating the multiclonal nature of BE. We conclude that recurrent and/or persistent BE after ablative therapy still contains genetic alterations associated with malignant progression to cancer. Therefore, the goal of treatment should be the complete elimination of Barrett's mucosa. ' 2005 Wiley-Liss, Inc.

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Section: Resultsmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Genomic analysis of Barrett's esophagus after ablative therapy: Persistence of genetic alterations at tumor suppressor loci

Hage

Siersema

Vissers

et al. 2005

Intl Journal of Cancer

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“…While several previous studies stated that patients with SSBE may develop dysplasia (Sharma et al, 1997) and EAC (Rudolph et al, 2000), some prospective studies have shown an increased risk of EAC development only in patients with LSBE (Weston et al, 1997;Hirota et al, 1999;Hage et al, 2004). Rudolph et al (2000) demonstrated that segment length was not related to cancer risk in a prospective cohort study of 309 Barrett's patients followed in the Seattle Barrett's Esophagus Project (P>0.2); however, when patients with HGD at entrance were excluded, a strong trend was observed, with a 5 cm difference in length associated with a 1.7-fold increase in cancer risk (95% confidence interval, 0.8-to 3.8-fold).…”

Section: Discussionmentioning

confidence: 99%

“…Hirota et al (1999) reported that the prevalence of dysplasia and cancer differed significantly in patients with SSBE vs patients with LSBE in a comprehensive prospective study of 889 consecutive patients. More recently, Hage et al (2004) reported a significantly increased risk of progression to HGD or EAC with LSBE after a mean follow-up of 12.7 years. Thus, it is likely that length of Barrett's epithelium is an important risk factor for both the prevalence of concurrent dysplasia and cancer and the incidence of future malignant progression.…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation of the nel-like 1 gene is a common and early event and is associated with poor prognosis in early-stage esophageal adenocarcinoma

et al. 2007

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The nel-like1 (NELL1) gene maps to chromosome 11p15, which frequently undergoes loss of heterozygosity in esophageal adenocarcinoma (EAC). NELL1 promoter hypermethylation was examined by real-time methylationspecific polymerase chain reaction in 259 human esophageal tissues. Hypermethylation of this promoter showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and EAC from normal esophagus (NE) (Po0.001). NELL1 normalized methylation values were significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's (D) and EAC than in NE (Po0.0000001). NELL1 hypermethylation frequency was zero in NE but increased early during neoplastic progression, to 41.7% in BE from patients with Barrett's alone, 52.5% in D and 47.8% in EAC. There was a significant correlation between NELL1 hypermethylation and BE segment length. Three (11.5%) of 26 ESCCs exhibited NELL1 hypermethylation. Survival correlated inversely with NELL1 hypermethylation in patients with stages I-II (P ¼ 0.0264) but not in stages III-IV (P ¼ 0.68) EAC. Treatment of KYSE220 ESCC and BIC EAC cells with 5-aza-2 0 -deoxycytidine reduced NELL1 methylation and increased NELL1 mRNA expression. NELL1 mRNA levels in EACs with an unmethylated NELL1 promoter were significantly higher than those in EACs with a methylated promoter (P ¼ 0.02). Promoter hypermethylation of NELL1 is a common, tissue-specific event in human EAC, occurs early during Barrett's-associated esophageal neoplastic progression, and is a potential biomarker of poor prognosis in early-stage EAC.

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Hypermethylation of the somatostatin promoter is a common, early event in human esophageal carcinogenesis

Jin

Mori

Hamilton

et al. 2007

Cancer

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BACKGROUND. The promoter of somatostatin (SST), a primary inhibitor of gastrin‐stimulated gastric acid secretion, is hypermethylated in 80% of human colon cancers. The aim of the current study was to investigate whether and at what stage promoter hypermethylation of SST is involved in human esophageal carcinogenesis. METHODS. SST promoter hypermethylation was examined by real‐time methylation‐specific polymerase chain reaction (PCR) (MSP) in 260 human esophageal tissue specimens. Real‐time reverse‐transcriptase PCR and MSP were also performed on esophageal cancer cell lines before and after treatment with 5‐aza‐2′‐deoxycytidine (5‐Aza‐dC). RESULTS. SST hypermethylation showed highly discriminative receiver‐operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinomas (ESCC) and esophageal adenocarcinomas (EAC) from normal esophagus (NE) (P < .01). Both SST methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett metaplasia without dysplasia or EAC (BE), low‐grade and high‐grade (HGD) dysplasia occurring in BE, EAC, and ESCC than in NE (P < .01). SST hypermethylation frequency was significantly lower in NE (9%) than in BE (70%), HGD (71.4%), or EAC (71.6%), whereas 14 (53.8%) of 26 ESCCs exhibited SST hypermethylation. There was a significant relation between SST hypermethylation and BE segment length, a known clinical risk factor for neoplastic progression. Demethylation of KYSE220 ESCC and OE33 EAC cells with 5‐Aza‐dC reduced SST methylation and increased SST mRNA expression. SST mRNA levels in native unmethylated EACs were significantly higher than in native methylated EACs (P < .05). CONCLUSIONS. SST promoter hypermethylation is a common event in human esophageal carcinomas and is related to early neoplastic progression in Barrett esophagus. Cancer 2008. © 2007 American Cancer Society.

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Oesophageal cancer incidence and mortality in patients with long-segment Barrett's Oesophagus after a mean follow-up of 12.7 years

Abstract: The annual risk of developing HGD or adenocarcinoma in patients with long-segment BO is 0.83%. Death due to adenocarcinoma is, however, uncommon, even in a cohort of patients with long-segment BO.

Cited by 97 publications

References 14 publications

Genomic analysis of Barrett's esophagus after ablative therapy: Persistence of genetic alterations at tumor suppressor loci

Genomic analysis of Barrett's esophagus after ablative therapy: Persistence of genetic alterations at tumor suppressor loci

Hypermethylation of the nel-like 1 gene is a common and early event and is associated with poor prognosis in early-stage esophageal adenocarcinoma

Hypermethylation of the somatostatin promoter is a common, early event in human esophageal carcinogenesis

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