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Connective tissue growth factor (CTGF) expression in endo-crine tumours is associated with high stromal expression of al-pha-smooth muscle actin.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
Manuscript (Other academic)
Identifiers
URN: urn:nbn:se:uu:diva-95945OAI: oai:DiVA.org:uu-95945DiVA, id: diva2:170333
Available from: 2007-05-16 Created: 2007-05-16 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Tumour Biological Factors Characterizing Metastasizing Serotonin-producing Ileocaecal Carcinoids
Open this publication in new window or tab >>Tumour Biological Factors Characterizing Metastasizing Serotonin-producing Ileocaecal Carcinoids
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this study, metastasizing serotonin-producing ileocaecal carcinoid tumours (MSPCs) were examined for biological characteristics that could be used to define clinically relevant subgroups within this patient population. Possible targets for new treatment options were also explored.

It was found that MSPCs share several biological characteristics such as expression of serotonin, tachykinins (TKs), chromogranin A, islet autoantigen-2 and connective tissue growth factor (CTGF). TKs and serotonin were demonstrated in the same endocrine tumours in the gut and lung. IA-2 expression was shown to be up-regulated in MSPCs, possibly in connection with active hormone secretion. CTGF expression was high in tumour areas adjacent to extensive stroma expressing alpha-smooth muscle actin. This indicated myofibroblast differentiation, which may be associated with fibrosis-related complications prevalent in patients with MSPCs. When compared with other endocrine tumours, MSPCs behaved as a relatively homogeneous group, though within the MSPC population several subgroups could be defined. Patients with tumours displaying either a solid growth pattern and/or a Ki67 index ≥1% had a less favourable prognosis than those who did not. Another group of patients, who had increased plasma TK concentrations, were more likely to suffer from severe diarrhea. This information should be considered when discussing clinical treatment and when undertaking tumour biological studies. New treatment possibilities, such as drugs that specifically target TK receptors and antibodies to CTGF, are also discussed.

In conclusion, MSPCs comprise a clinically relevant tumour group with similar biological features that are distinct from other endocrine tumours. Subgroups of patients within this patient category can be defined which may be relevant when establishing prognosis and when selecting future treatment modalities.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. p. 45
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 264
Keywords
Internal medicine, endocrine tumour, midgut carcinoid, serotonin-producing neuroendocrine carcinoma, prognosis, morphology, tachykinin, connective tissue growth factor, islet autoantigen-2, morphology, carcinoid syndrome, Invärtesmedicin
Identifiers
urn:nbn:se:uu:diva-7906 (URN)978-91-554-6906-1 (ISBN)
Public defence
2007-09-01, Rudbecksalen, Rudbeck Laboratory, Dag Hammarskjölds väg 20, Uppsala, 09:30
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Supervisors
Available from: 2007-05-16 Created: 2007-05-16Bibliographically approved

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