Flow cytometric DNA analysis and p53 protein expression show a good correlation with histologic findings in patients with barrett's esophagus

Abstract

BACKGROUND There is a considerable degree of subjectivity and, therefore, substantial interobserver and intraobserver disagreement in the diagnosis and grading of dysplastic lesions in Barrett's esophagus (BE). The aim of this study was to evaluate the usefulness of DNA flow cytometry and immunohistochemical staining for p53 protein as objective methods to complement the conventional histologic diagnosis of dysplasia in patients with this disease. The most common problems and the possible advantages of using these procedures are analyzed briefly in this article. METHODS Formalin fixed, paraffin embedded tissue from 55 patients diagnosed with BE were processed for flow cytometric measurements (ploidy and proliferation index) and p53 immunostaining. RESULTS Both the cytometric data and the positivity of staining for p53 revealed a statistically significant increase throughout the following sequence: no dysplasia → indefinite for dysplasia → low grade dysplasia → high grade dysplasia → adenocarcinoma. There was also a highly significant correlation between the results of the cytometric study and the positivity of staining for p53. CONCLUSIONS In the future, the use of this procedure could play an important role in the evaluation of patients with BE. Considering that staining for p53 is technically simple, economical, and quick, and the materials required are available to most pathology laboratories, this method appears to be a firm candidate for application as a biomarker in BE. The authors have shown that it is possible to obtain adequate results for cytometric analysis with small formalin fixed, paraffin embedded biopsies if a strict protocol for the acceptance of tissue samples and/or histograms is observed. Cancer 1998;83:641‐651. © 1998 American Cancer Society.

p53 Immunohistochemistry as a biomarker of dysplasia and neoplastic progression in Barrett's oesophagus

“…p53 was a more powerful predictor of progression than LGD (RR 4.5 vs 2.4), but the two combined yielded a relative risk of 11.2. Importantly, in the Gimenez study 53 indefinite for dysplasia showing p53-positivity was much more likely to progress than if negative (5/7 vs 1/10). In Kaye et al 9 status of this group was not specifically provided but, currently, of LGD and ID cases which had sufficient material for p53 staining and follow up, 14/20 p53-positives progressed vs 3/12 p53-negatives (unpublished data).…”

Evaluation of p53 mutations in premalignant esophageal lesions and esophageal adenocarcinoma using laser capture microdissection

“…This is probably due to the purity of our cell population obtained by selection of specific cells by LCM, and direct sequencing of PCR products in both directions, rather than using indirect techniques. 7,12,15,16,18,[23][24][25][26][27][28][29] Therefore, the role of p53 mutation as a prognostic factor in progression of metaplastic BE toward esophageal adenocarcinoma is not certain. Since the molecular basis of p53 function and mutations is not fully understood, a better evaluation of the biological properties of different p53 mutations is needed in order to interpret the results.…”

Selectively Advantageous Mutations and Hitchhikers in Neoplasms

“…The evolution of clones that we report here is also consistent with neoplasia, and recognition of BE as a benign neoplasm may improve our understanding of the basis for its precancerous potential. The study of evolution requires measurement of changes in allele frequencies, and we did not assess the relationship between genotypes and dysplastic phenotypes because the two were generated on different samples that could not be directly compared quantitatively, although the relationships among p16, p53, and cytometric abnormalities and dysplasia have been published previously by us and others (2,17,18,25,69,(82)(83)(84)(85)(86).…”