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Tumour Biological Factors Characterizing Metastasizing Serotonin-producing Ileocaecal Carcinoids

Cunningham, Janet Lynn, 1974- (author)
Uppsala universitet,Institutionen för medicinska vetenskaper
Janson, Eva Tiensuu (thesis advisor)
Öberg, Kjell (thesis advisor)
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Modlin, Irvin M., Dr. (opponent)
Yale University School of Medicine, New Haven, CT
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 (creator_code:org_t)
ISBN 9789155469061
Uppsala : Acta Universitatis Upsaliensis, 2007
English 45 s.
Series: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 264
  • Doctoral thesis (other academic/artistic)
Abstract Subject headings
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  • 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.

Keyword

Internal medicine
endocrine tumour
midgut carcinoid
serotonin-producing neuroendocrine carcinoma
prognosis
morphology
tachykinin
connective tissue growth factor
islet autoantigen-2
morphology
carcinoid syndrome
Invärtesmedicin

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vet (subject category)
dok (subject category)

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