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Characterization of colon carcinoma growth pattern by computerized morphometry: definition of a complexity index
Örebro University, School of Health and Medical Sciences.
2008 (English)In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 22, no 4, p. 465-472Article in journal (Refereed) Published
Abstract [en]

The invasive front of carcinomas may vary in complexity from smooth to highly complex when the front splits up into small cell clusters or even single cancer cells. The degree of complexity is usually estimated visually and semiquantitatively by a pathologist, although more objective methods based on computer-assisted image analysis are available. In this study, we compared the visual estimation of the irregularity of the tumour invasion front of colon carcinomas to different quantitative image analytical techniques and defined a complexity index for the invasive margin. Sections from 29 archived colon carcinomas were stained immunohistochemically for cytokeratin 8. Images of the tumour invasion front were read into a computer and thresholded so that the tumour tissue became black and the background white or so that the tumour front was outlined by a single pixel line. The invasive front was visually classified into four degrees of irregularity by a pathologist. The complexity of the front was then assessed using four different image analysis techniques, i.e. the estimation of fractal dimension, tumour front length, number of tumour cell clusters and lacunarity. Fractal dimension and tumour cell clusters together gave the best correlation to visual grading using a discriminant analysis. A cluster analysis and a tree diagram analysis were then performed and were found to be superior to visual estimation. The clusters represent different degrees of complexity and the result of the tree diagram analysis can be used to assign complexity indices to colon tumours. The fractal dimension separated tumours up to a certain level (1.5-1.6) of complexity. When the tumour front split up into small cell clusters, the counting of tumour cell clusters separated the cells over and above the fractal dimension. This new technique can be used to objectively and quantitatively describe the complexity of the invasive front of tumours.

Place, publisher, year, edition, pages
2008. Vol. 22, no 4, p. 465-472
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-3031DOI: 10.3892/ijmm_00000044PubMedID: 18813853OAI: oai:DiVA.org:oru-3031DiVA, id: diva2:136459
Available from: 2008-11-10 Created: 2008-11-10 Last updated: 2017-12-14Bibliographically 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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Franzén, Lennart E.Hahn-Strömberg, VictoriaBodin, Lennart

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