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Aberrant nuclear localization of beta-catenin without genetic alterations in beta-catenin or Axin genes in esophageal cancer.

Kudo J, Nishiwaki T, Haruki N, Ishiguro H, Shibata Y, Terashita Y, Sugiura H, Shinoda N, Kimura M, Kuwabara Y, Fujii Y - World J Surg Oncol (2007)

Bottom Line: Samples were obtained from 50 esophageal cancer patients.Overexpression of cyclin D1 was observed in 27 out of 50 (54%) patients.Sequencing analysis of the Axin cDNA revealed only a splicing variant (108 bp deletion, position 2302-2409) which was present in the paired normal mucosa.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan. dr_kudo@yahoo.co.jp

ABSTRACT

Background: beta-catenin is a multifunctional protein involved in two apparently independent processes: cell-cell adhesion and signal transduction. beta-catenin is involved in Wnt signaling pathway that regulates cellular differentiation and proliferation. In this study, we investigated the expression pattern of beta-catenin and cyclin D1 using immunohistochemistry and searched for mutations in exon 3 of the beta-catenin gene and Axin gene in esophageal squamous cell carcinoma.

Materials and methods: Samples were obtained from 50 esophageal cancer patients. Immunohistochemical staining for beta-catenin and cyclin D1 was done. Mutational analyses of the exon3 of the beta-catenin gene and Axin gene were performed on tumors with nuclear beta-catenin expression.

Results: Four (8%) esophageal cancer tissues showed high nuclear beta-catenin staining. Overexpression of cyclin D1 was observed in 27 out of 50 (54%) patients. All four cases that showed nuclear beta-catenin staining overexpressed cyclin D1. No relationship was observed between the expression pattern of beta-catenin and cyclin D1 and age, sex, tumor size, stage, differentiation grade, lymph node metastasis, response to chemotherapy, or survival. No mutational change was found in beta-catenin exon 3 in the four cases with nuclear beta-catenin staining. Sequencing analysis of the Axin cDNA revealed only a splicing variant (108 bp deletion, position 2302-2409) which was present in the paired normal mucosa.

Conclusion: A fraction of esophageal squamous cell carcinomas have abnormal nuclear accumulation of beta-catenin accompanied with increased cyclin D1 expression. Mutations in beta-catenin or axin genes are not responsible for this abnormal localization of beta-catenin.

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Immunohistochemical staining of β-catenin in normal and cancer tissues of the esophagus. In this cancer tissues, β-catenin was expressed in the nuclei, and was hardly detectable at the plasma membrane (a). In normal esophageal epithelium, β-catenin was expressed at the cell membrane (b).
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Figure 1: Immunohistochemical staining of β-catenin in normal and cancer tissues of the esophagus. In this cancer tissues, β-catenin was expressed in the nuclei, and was hardly detectable at the plasma membrane (a). In normal esophageal epithelium, β-catenin was expressed at the cell membrane (b).

Mentions: Fifty esophageal cancer tissues and paired normal esophageal mucosa were stained for β-catenin using immunohistochemistry. In all the normal esophageal mucosa, β-catenin staining was restricted to the plasma membrane. The intensity of the staining did not vary very much among individuals. In most of the 50 esophageal cancer tissues, the β-catenin staining was at the plasma membrane. However, four cases (8%) of esophageal cancer tissue were judged as showing widespread nuclear staining. And in these cases, β-catenin was not expressed on the plasma membrane (Fig. 1a). Normal esophageal mucosa of these cases showed membrane staining of β-catenin, and did not show nuclear staining (Fig. 1b). 46 other esophageal cancer samples showed either plasma membrane or cytoplasmic staining or both. No relationship was observed between β-catenin expression pattern and age, sex, tumor size, stage, differentiation grade, lymph node metastasis, response to chemotherapy, or survival (χ-square test, Table 2).


Aberrant nuclear localization of beta-catenin without genetic alterations in beta-catenin or Axin genes in esophageal cancer.

Kudo J, Nishiwaki T, Haruki N, Ishiguro H, Shibata Y, Terashita Y, Sugiura H, Shinoda N, Kimura M, Kuwabara Y, Fujii Y - World J Surg Oncol (2007)

Immunohistochemical staining of β-catenin in normal and cancer tissues of the esophagus. In this cancer tissues, β-catenin was expressed in the nuclei, and was hardly detectable at the plasma membrane (a). In normal esophageal epithelium, β-catenin was expressed at the cell membrane (b).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1808060&req=5

Figure 1: Immunohistochemical staining of β-catenin in normal and cancer tissues of the esophagus. In this cancer tissues, β-catenin was expressed in the nuclei, and was hardly detectable at the plasma membrane (a). In normal esophageal epithelium, β-catenin was expressed at the cell membrane (b).
Mentions: Fifty esophageal cancer tissues and paired normal esophageal mucosa were stained for β-catenin using immunohistochemistry. In all the normal esophageal mucosa, β-catenin staining was restricted to the plasma membrane. The intensity of the staining did not vary very much among individuals. In most of the 50 esophageal cancer tissues, the β-catenin staining was at the plasma membrane. However, four cases (8%) of esophageal cancer tissue were judged as showing widespread nuclear staining. And in these cases, β-catenin was not expressed on the plasma membrane (Fig. 1a). Normal esophageal mucosa of these cases showed membrane staining of β-catenin, and did not show nuclear staining (Fig. 1b). 46 other esophageal cancer samples showed either plasma membrane or cytoplasmic staining or both. No relationship was observed between β-catenin expression pattern and age, sex, tumor size, stage, differentiation grade, lymph node metastasis, response to chemotherapy, or survival (χ-square test, Table 2).

Bottom Line: Samples were obtained from 50 esophageal cancer patients.Overexpression of cyclin D1 was observed in 27 out of 50 (54%) patients.Sequencing analysis of the Axin cDNA revealed only a splicing variant (108 bp deletion, position 2302-2409) which was present in the paired normal mucosa.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan. dr_kudo@yahoo.co.jp

ABSTRACT

Background: beta-catenin is a multifunctional protein involved in two apparently independent processes: cell-cell adhesion and signal transduction. beta-catenin is involved in Wnt signaling pathway that regulates cellular differentiation and proliferation. In this study, we investigated the expression pattern of beta-catenin and cyclin D1 using immunohistochemistry and searched for mutations in exon 3 of the beta-catenin gene and Axin gene in esophageal squamous cell carcinoma.

Materials and methods: Samples were obtained from 50 esophageal cancer patients. Immunohistochemical staining for beta-catenin and cyclin D1 was done. Mutational analyses of the exon3 of the beta-catenin gene and Axin gene were performed on tumors with nuclear beta-catenin expression.

Results: Four (8%) esophageal cancer tissues showed high nuclear beta-catenin staining. Overexpression of cyclin D1 was observed in 27 out of 50 (54%) patients. All four cases that showed nuclear beta-catenin staining overexpressed cyclin D1. No relationship was observed between the expression pattern of beta-catenin and cyclin D1 and age, sex, tumor size, stage, differentiation grade, lymph node metastasis, response to chemotherapy, or survival. No mutational change was found in beta-catenin exon 3 in the four cases with nuclear beta-catenin staining. Sequencing analysis of the Axin cDNA revealed only a splicing variant (108 bp deletion, position 2302-2409) which was present in the paired normal mucosa.

Conclusion: A fraction of esophageal squamous cell carcinomas have abnormal nuclear accumulation of beta-catenin accompanied with increased cyclin D1 expression. Mutations in beta-catenin or axin genes are not responsible for this abnormal localization of beta-catenin.

Show MeSH
Related in: MedlinePlus