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Disturbed expression of E-cadherin, beta-catenin and tight junction proteins in colon carcinoma is unrelated to growth pattern and genetic polymorphisms
Örebro University, School of Health and Medical Sciences.
2008 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 4, p. 253-262Article in journal (Refereed) Published
Abstract [en]

Adhesion proteins are responsible for the structural integrity of epithelial tissue and in tumors this integrity is often lost, resulting in a disorganization of the tissue. In the present study the complexity of the invasive front of colon carcinomas was correlated with cell adhesion protein expression and with polymorphisms in their genes. A complexity index was constructed from 32 colon carcinomas using computer-assisted morphometry estimating fractal dimension and tumor cell clusters followed by tree analysis. Immunohistochemical staining of beta-catenin, E-cadherin, occludin and claudin 2 was used for assessment of protein expression. Genetic screening of tissue from the tumor invasion front with laser microdissection was performed using SSCP and DNA sequencing. Adhesion protein distribution was significantly disturbed in most carcinomas. A single mutation in the gene of beta-catenin was found but there was no correlation between protein expression and genetic polymorphism. Nor was there any correlation between the complexity of the invasive border and protein distribution or genetic alterations. The results indicate that the complexity of colon carcinoma invasion is not dependent on genetic derangements in the genes of adhesion proteins or the protein distribution. Rather, aberrations in the function of other proteins related to the adhesive proteins could be responsible.

Place, publisher, year, edition, pages
2008. Vol. 116, no 4, p. 253-262
Keywords [en]
patology, molecular cell biology
National Category
Medical and Health Sciences Cell and Molecular Biology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-3032DOI: 10.1111/j.1600-0463.2008.00894.xPubMedID: 18397460OAI: oai:DiVA.org:oru-3032DiVA, id: diva2:136460
Available from: 2008-11-10 Created: 2008-11-10 Last updated: 2018-01-13Bibliographically approved
In thesis
1. Cell adhesion proteins in different invasive patterns of colon carcinomas: a morphometric and molecular genetic study
Open this publication in new window or tab >>Cell adhesion proteins in different invasive patterns of colon carcinomas: a morphometric and molecular genetic study
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Colorectal carcinoma is the second most common type of cancer in both men and women in Sweden. Cancer of the colon and rectum are often considered together and their ten year survival rate is approximately 50 – 60 % depending on sex and location. Different histopathological characteristics of such cancers, including the complexity of growth, are of importance for prognosis.

This thesis has compared different morphometric methods in order to achieve a quantitative and objective measurement of the invasive front of colon carcinoma. Since the growth pattern is dependent on the cell adhesiveness of different proteins we studied the distribution and localization of E-cadherin, Beta-catenin, Claudin 1,2,7 and Occludin as well as screened the genes for mutations.

We found a perturbed protein expression of E-cadherin, Beta-catenin, Claudin 1,2,7 and Occludin in tumor sections compared to normal mucosa, but no relation to tumor volume or growth pattern could be seen. The tumor volume was found to be correlated to the growth pattern but not responsible to the perturbed protein expression. In the mutation screening we found a SNP in exon 13 the E-cadherin gene in the tumor, as well as in exon 2 of Claudin 1 and exon 4 of Claudin 7 in both tumor and normal mucosa. No correlation between mutations and growth pattern or tumor volume was found.

In conclusion, this thesis shows that the computer image analysis with estimation of fractal dimension and number of free tumor cell clusters is superior to the semi quantitative visual grading of tumor invasive complexity. The aberrant expression of cell adhesion proteins in the tumor compared to normal mucosa as well as polymorphisms in the cell adhesion genes CLDN1 and CLDN7 in both tumor and normal mucosa can suggest that these aberrations are important in the tumorigenesis of colon carcinoma.

 

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2008. p. 61
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 24
Keywords
colon carcinoma, growth pattern, tight junction, Complexity Index, cell adhesion, E-cadherin, Beta-catenin, Occludin, Claudin.
National Category
Clinical Science
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-2603 (URN)978-91-7668-640-9 (ISBN)
Public defence
2008-11-28, Wilandersalen, USÖ, Universitetsjukhuset, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2008-11-10 Created: 2008-11-10 Last updated: 2017-10-18Bibliographically approved

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Hahn-Strömberg, VictoriaBodin, Lennart

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