Apoptotic and proliferative activity in the neoplastic progression of Barrett's oesophagus: a comparative study

Whittles, CE; Biddlestone, L.; Burton, Andrea; Barr, Hugh; Jankowski, Janusz; Warner, Philip J.; Shepherd, Neil A.

doi:10.1002/(sici)1096-9896(199904)187:5<535::aid-path302>3.0.co;2-g

Cited by 74 publications

(40 citation statements)

References 22 publications

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“…The most common histological type of esophageal cancer is the squamous cell carcinoma or epidermoid carcinoma; historically, adenocarcinoma is less frequent (27) . However, several studies have shown that the incidence of adenocarcinoma has been increasing in western countries (5,27,36,37) , whereas the incidence of epidermoid carcinoma has remained relatively stable (36) . The reason why such increase occurs is controversial; according to some authors, the lower prevalence of Helicobacter pylori infection, which seems to be a protective factor, and the higher prevalence of obesity, increased fat intake, and smoking may be involved (5,36) .…”

Section: Discussionsupporting

confidence: 91%

“…It is still unclear whether histological types differ as to location only or as to biological behavior as well (1) . Barrett's esophagus is a premalignant condition associated with gastroesophageal refl ux, where the esophageal squamous epithelium is replaced by a metaplastic columnar epithelium (37) . Gastroesophageal refl ux has been suggested as an etiologic factor for adenocarcinoma and gastric cardia cancer as well (36) , which results in their being studied as a single entity (27) .…”

Section: Discussionmentioning

confidence: 99%

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Prevalence of p21 immunohistochemical expression in esophageal adenocarcinoma

Villwock

Meurer

Cavazzola

et al. 2006

Arq. Gastroenterol.

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-Background -In western societies, the prevalence of adenocarcinoma of the gastroesophageal junction has increased in recent years. It is commonly accepted today that esophageal adenocarcinoma develops from a premalignant lesion: Barrett's esophagus. This type of carcinoma is hardly diagnosed at early stages, which results in signifi cant mortality. Molecular biology studies have shown that most malignant tumors originate from the interaction between inherited characteristics and external factors, which may cause genetic changes that interfere with the control over the differentiation and growth of cells in susceptible individuals. p21 (WAF1/CIP1) has a key role in the regulation of the cell cycle, and its immunohistochemical expression has been investigated in several tumors, showing that it infl uences the prognosis of various neoplasms. Aim -To check the prevalence of p21 protein expression in patients with esophageal adenocarcinoma diagnosed in the last 5 years by the Group for Surgeries of the Esophagus and Stomach of "Hospital de Clínicas de Porto Alegre", RS, Brazil. Methods -The study population consisted of 42 patients with esophageal adenocarcinoma diagnosed by the Group for Surgeries of the Esophagus and Stomach between January 1998 and December 2002. The expression of p21 protein was determined by immunohistochemistry using primary antibody, p21, clone SX118, code M7202 (Dako), and assessed according to the immunoreactive scoring system. Results -Of 42 analyzed patients, 83.3% were male and older than 40 years. Among these, 56.2% were submitted to curative resection: total gastrectomy and transhiatal esophagogastrectomy. The remaining patients were submitted to palliative surgery or did not undergo any surgical treatment. Only fi ve patients received adjuvant chemotherapy and radiation therapy, either alone or combined. Advanced disease (stages III and IV) was detected in 78.6% of the patients. Only nine patients were positive for p21, according to the immunoreactive scoring system. Conclusion -p21 was expressed in 9 of 42 patients (21.4%) with esophageal adenocarcinoma diagnosed in the last 5 years by the Group for Surgeries of the Esophagus and Stomach of Hospital de Clínicas de Porto Alegre. In our patient population, the accumulation of p21 did not play a key role in the carcinogenesis of esophageal adenocarcinoma. HEADINGS -Esophageal neoplasms. Adenocarcinoma. Cyclin-dependent kinase inhibitor p21.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Prevalence of p21 immunohistochemical expression in esophageal adenocarcinoma

Villwock

Meurer

Cavazzola

et al. 2006

Arq. Gastroenterol.

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“…Although the original Ki-67 antibody was reactive only in frozen sections, a newer antibody to an epitope of Ki-67 (Mib-1) is active in formalin-fixed, paraffin-embedded tissues. It has therefore been used extensively to evaluate malignancies in many different organ sites (15)(16)(17)(18)(19)(20)(21)(22).…”

Section: Discussionmentioning

confidence: 85%

Direct Correlation between Proliferative Activity and Dysplasia in Pancreatic Intraepithelial Neoplasia (PanIN): Additional Evidence for a Recently Proposed Model of Progression

et al. 2002

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The genetic alterations present in PanINs have been extensively studied. PanINs have been examined for loss of heterozygosity at a number of loci and for alterations in several genes such as p16, p53, DPC4,. These genetic studies, along with histologic observations, support a progression model for pancreatic neoplasia in which increasing histologic grades of PanIN are associated with the accumulation of genetic alterations in cancer-associated genes ( Fig. 1) (11).

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“…These data are in agreement with other groups' results regarding clonal genetic alterations (van Dekken et al, 1999) in Barrett's epithelium, pointing out that new and advanced methods (Whittles et al, 1999) may help in evaluating the cancerogenic potential of Barrett's metaplasia and that of squamous tissue next to metaplastic and/or dysplastic epithelium (Barrett et al, 1999;Dolan et al, 2000).…”

Section: Romagnoli Et Almentioning

confidence: 99%

Molecular Alterations of Barrett's Esophagus on Microdissected Endoscopic Biopsies

Romagnoli

Roncalli

Graziani

et al. 2001

Laboratory Investigation

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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).

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Apoptotic and proliferative activity in the neoplastic progression of Barrett's oesophagus: a comparative study

Cited by 74 publications

References 22 publications

Prevalence of p21 immunohistochemical expression in esophageal adenocarcinoma

Prevalence of p21 immunohistochemical expression in esophageal adenocarcinoma

Direct Correlation between Proliferative Activity and Dysplasia in Pancreatic Intraepithelial Neoplasia (PanIN): Additional Evidence for a Recently Proposed Model of Progression

Molecular Alterations of Barrett's Esophagus on Microdissected Endoscopic Biopsies

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