Abstract |
In Barrett's mucosa, both aneuploidy and TP53 mutations are consistently recognized as markers of an increased risk of Barrett's adenocarcinoma. Overexpression of the mitotic kinase encoding gene ( AURKA) results in chromosome instability (assessed from the micronuclei count) and ultimately in aneuploidy. Eighty-seven esophageal biopsy samples representative of all the phenotypic lesions occurring in the multistep process of Barrett's carcinogenesis (gastric metaplasia in 25, intestinal metaplasia in 25, low-grade intraepithelial neoplasia in 16, high-grade intraepithelial neoplasia in 11, and Barrett's adenocarcinoma in 10) were obtained from long segments of Barrett's mucosa. Twenty-five additional biopsy samples of native esophageal mucosa were used for control purposes. In all tissue samples, the immunohistochemical expression of both AURKA and TP53 gene products was scored; and the micronuclei index was calculated. AURKA immunostaining increased progressively and significantly along with dedifferentiation of the histologic phenotype (P < .001). Nine of 10 Barrett's adenocarcinomas showed AURKA immunostaining. AURKA expression correlated significantly with p53 expression and the micronuclei index (both Ps < .001). AURKA overexpression is significantly associated with Barrett's mucosa progressing to Barrett's adenocarcinoma and contributes to esophageal carcinogenesis via chromosome instability. The identification of AURKA as a novel molecular target of cancer progression in Barrett's mucosa provides a lead for the development of new therapeutic approaches in Barrett's mucosa patients.
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Authors | Massimo Rugge, Matteo Fassan, Giovanni Zaninotto, Marco Pizzi, Luciano Giacomelli, Giorgio Battaglia, Christian Rizzetto, Paola Parente, Ermanno Ancona |
Journal | Human pathology
(Hum Pathol)
Vol. 41
Issue 10
Pg. 1380-6
(Oct 2010)
ISSN: 1532-8392 [Electronic] United States |
PMID | 20656315
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2010 Elsevier Inc. All rights reserved. |
Chemical References |
- TP53 protein, human
- Tumor Suppressor Protein p53
- AURKA protein, human
- Aurora Kinase A
- Aurora Kinases
- Protein Serine-Threonine Kinases
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Topics |
- Adenocarcinoma
(enzymology, pathology)
- Aurora Kinase A
- Aurora Kinases
- Barrett Esophagus
(enzymology, pathology)
- Carcinoma in Situ
(enzymology, pathology)
- Cell Nucleus Size
- Cell Transformation, Neoplastic
(metabolism, pathology)
- Esophageal Neoplasms
(enzymology, pathology)
- Esophagus
(enzymology, pathology)
- Gastric Mucosa
(enzymology, pathology)
- Humans
- Immunohistochemistry
- Intestinal Mucosa
(enzymology, pathology)
- Metaplasia
- Mucous Membrane
(enzymology, pathology)
- Oligonucleotide Array Sequence Analysis
- Protein Serine-Threonine Kinases
(biosynthesis)
- Retrospective Studies
- Tumor Suppressor Protein p53
(biosynthesis)
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