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Malignant ileocaecal serotonin-producing carcinoid tumours: the presence of a solid growth pattern and/or Ki67 index above 1% identifies patients with a poorer prognosis
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. (Onkologisk endokrinologi)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
Christian Medical College, Vellore, India. (Onkologisk endokrinologi)
Vise andre og tillknytning
2007 (engelsk)Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 46, nr 6, s. 747-756Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Patients with malignant serotonin-producing carcinoid tumours in the jejunum, ileum and caecum generally have long survival expectancy. In some patients, however, tumour progression is more rapid and there is a need to identify them at an early stage. The purpose of this study was to determine if histopathological characteristics and/or Ki67 and apoptotic indices are of prognostic value in cases of metastatic disease. Eighty-one patients with this tumour were included in the study; all had metastases and their survival range was 1-223 months. Five growth patterns were identified and described. For 57 patients whose tumour material was available, the Ki67 and apoptotic indices were calculated for ten randomly selected tumour areas and 'hot spots'. A Cox regression analysis was used to test if histopathology and/or Ki67 index ≥1% could identify patients whose survival might be shorter than anticipated. One of the histopathological growth patterns-the solid (non-organoid) cell pattern-was correlated to shorter survival in both primary tumours and metastases, when compared with the organoid growth patterns (hazard ratio 2.9 and 2.3, p≤0.01). In 75% of primary tumours and 67% of metastases, the average Ki67 index was<0.5%. Ki67 index in 'hot spots' ranged from 0.1 to 14%. Ki67 index ≥1%, in both primary tumour and metastases, identified patients at increased risk of shorter survival (hazard ratio 5.4 and 2.5, p≤0.01). The apoptotic index was very low in all cases. We conclude that in patients with metastazising serotonin-producing carcinoids, two independent criteria, a solid growth pattern and Ki67 index ≥1%, can be used to identify patients with a poorer prognosis. This study also showed that Ki67 index <2% cannot, as previously suggested, be used to indicate a benign progression for this tumour category.

sted, utgiver, år, opplag, sider
2007. Vol. 46, nr 6, s. 747-756
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-95943DOI: 10.1080/02841860701218659ISI: 000248032100006PubMedID: 17653896OAI: oai:DiVA.org:uu-95943DiVA, id: diva2:170331
Tilgjengelig fra: 2007-05-16 Laget: 2007-05-16 Sist oppdatert: 2017-12-14bibliografisk kontrollert
Inngår i avhandling
1. Tumour Biological Factors Characterizing Metastasizing Serotonin-producing Ileocaecal Carcinoids
Åpne denne publikasjonen i ny fane eller vindu >>Tumour Biological Factors Characterizing Metastasizing Serotonin-producing Ileocaecal Carcinoids
2007 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2007. s. 45
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 264
Emneord
Internal medicine, endocrine tumour, midgut carcinoid, serotonin-producing neuroendocrine carcinoma, prognosis, morphology, tachykinin, connective tissue growth factor, islet autoantigen-2, morphology, carcinoid syndrome, Invärtesmedicin
Identifikatorer
urn:nbn:se:uu:diva-7906 (URN)978-91-554-6906-1 (ISBN)
Disputas
2007-09-01, Rudbecksalen, Rudbeck Laboratory, Dag Hammarskjölds väg 20, Uppsala, 09:30
Opponent
Veileder
Tilgjengelig fra: 2007-05-16 Laget: 2007-05-16bibliografisk kontrollert

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