p53 immunoexpression: An aid to conventional methods in the screening of precursor lesions of squamous esophageal cancer in patients at high-risk?

Fagundes, Renato Borges; Melo, Carlos R.; Pütten, Antonio Carlos Kruel; Moreira, Luís Fernando; Barros, Sérgio Gabriel Silva de

doi:10.1016/j.cdp.2005.01.003

Cited by 11 publications

(12 citation statements)

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“…Also overexpression of choline kinase, which forms PC, is observed in several cancers (30). The immunohistochemical markers used [p53 mutations and cell proliferation (Ki-67)] are widely used by histopathologists in the diagnosis and assessment of dysplasia in Barrett's esophagus (31) and squamous neoplasia (32). Normal epithelial cells transformed by oncoproteins or loss of tumor suppressors also show increases in PC, and conversely, reintroduction of p53 into p53 −/− (HCT116) cells has been shown to decrease intracellular PC levels (33).…”

Section: Discussionmentioning

confidence: 99%

Metabolic Profiling Detects Field Effects in Nondysplastic Tissue from Esophageal Cancer Patients

et al. 2010

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The variable rate of missed cancer in endoscopic biopsies and lack of other biomarkers reduce the effectiveness of surveillance programs in esophageal cancer. Based on the "field cancerization" hypothesis that tumors arise within a transformed field with an altered biochemical phenotype, we sought to test if metabolic profiling could differentiate between histologically normal tissue from individuals with and without esophageal cancer. Thirty-five patients with esophageal adenocarcinoma and 52 age-matched controls participated in the study. Using 1 H magic angle spinning-nuclear magnetic resonance spectroscopy of intact tissue, we generated metabolic profiles of tumor tissue, proximal histologically normal mucosa from cancer patients (PHINOM), and proximal histologically normal mucosa from a control group. Using multivariate regression and receiveroperator characteristic analysis, we identified a panel of metabolites discriminating malignant and histologically normal tissues from cancer patients and from that of controls. Whereas 26% and 12% of the spectral profile regions were uniquely discriminating tumor or control tissue, respectively, 5% of the profile exhibited a significant progressive change in signal intensity from controls to PHINOM to tumor. Regions identified were assigned to phosphocholine (PC), glutamate (Glu), myo-inositol, adenosine-containing compounds, uridine-containing compounds, and inosine. In particular, the PC/Glu ratio in histologically normal tissue signified the presence of esophageal cancer (n = 123; area under the curve, 0.84; P < 0.001). In conclusion, our findings support the hypothesis of the presence of metabonomic field effects in esophageal cancer, even in non-Barrett's segments. This indicates that metabolic profiling of tissue can potentially play a role in the surveillance of cancer by reporting on the phenotypic consequences of field cancerization. Cancer Res; 70(22); 9129-36. ©2010 AACR.

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Section: Discussionmentioning

confidence: 99%

Metabolic Profiling Detects Field Effects in Nondysplastic Tissue from Esophageal Cancer Patients

et al. 2010

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“…Gastroesophageal reflux causes inflammation and may explain the positive reactivity of p53 in these patients. However, inflammatory alterations are closely related to the process of esophageal carcinogenesis, and are capable of modifying the function of many proteins that regulate the cell cycle, such as p53 51,55 …”

Section: Discussionmentioning

confidence: 99%

P53 and Ki-67 overexpression in gastroesophageal reflux disease - Barrett's esophagus and adenocarcinoma sequence

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Fagundes

et al. 2009

Diseases of the Esophagus

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Gastroesophageal reflux disease (GERD) is a major risk factor for the development of esophageal adenocarcinoma (ACE). Many molecular alterations occur in esophageal carcinogenesis, yet the exact mechanism of ACE development remains unknown. This study aims to determine p53 protein and Ki-67 expression in esophageal mucosa of patients with GERD and study the correlation between these markers and the progression from normal squamous epithelium to esophagitis, columnar epithelium with or without intestinal metaplasia and ACE. We analyzed p53 protein and Ki-67 expression in biopsies of 200 patients with GERD and 35 patients with ACE. Those biopsies were classified into five groups: (i) G1 normal squamous epithelium (58); (ii) G2 esophagitis (80); (iii) G3 columnar epitheliums without intestinal metaplasia (30); (iv) G4, columnar epitheliums with intestinal metaplasia (32); and (v) G5 ACEs (35). p53 protein overexpression was found in 7% (4) of G1, 37.5% (30) of G2, 30% (9) of G3, 62.5% (20) of G4, and 71.4% (25) of G5 (p < 0.001). Ki-67 index increased according to the severity of histopathological diagnoses. Ki67 index was 21.3 +/- 19.5% in G1, 38.8 +/- 24.9% in G2, 37.7 +/- 26.3% in G3, 52.8 +/- 24.6% in G4, and 57.1 +/- 25.1% in G5 (P < 0.001). Linear correlation between p53/Ki67 expression and the multistep progression from squamous epithelium to ACE was observed (P < 0.001 and P < 0.05). Our results indicate that overexpression of p53 and increased Ki-67 could be associated with the development and progression to ACE in patients with GERD.

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“…On the basis of the results of Fagundes et al, 21,22 we calculated that it would require 134 patients to detect a 17% positivity of p53 expression in esophageal mucosa of high-risk individuals, considering a statistical power of 90% and a confidence interval of 95%. Data analysis was conducted with SPSS (Chicago, Illinois, U.S.A.).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies suggested that its expression in biopsies of individuals at risk for SCCE could be useful to identify subjects with greater risk for SCCE. 21,22 Therefore, we chose to study the expression of p53 protein as a potential marker in cells sampled, through an exfoliative cytology technique, from individuals with risk factors for SCCE.…”

Section: Discussionmentioning

confidence: 99%

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Detecting p53 Immunoexpression inEsophageal Mucosa with Exfoliative Cytologyin Individuals at Risk for Squamous CellCarcinoma of the Esophagus

et al. 2010

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p53 immunoexpression: An aid to conventional methods in the screening of precursor lesions of squamous esophageal cancer in patients at high-risk?

Cited by 11 publications

References 20 publications

Metabolic Profiling Detects Field Effects in Nondysplastic Tissue from Esophageal Cancer Patients

Metabolic Profiling Detects Field Effects in Nondysplastic Tissue from Esophageal Cancer Patients

P53 and Ki-67 overexpression in gastroesophageal reflux disease - Barrett's esophagus and adenocarcinoma sequence

Detecting p53 Immunoexpression inEsophageal Mucosa with Exfoliative Cytologyin Individuals at Risk for Squamous CellCarcinoma of the Esophagus

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