| 1. |
- Ekeblad, Sara, et al.
(författare)
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Gastrointestinal stromal tumors express the orexigen ghrelin
- 2006
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Ingår i: Endocrine-related cancer. - : Bioscientifica. - 1351-0088 .- 1479-6821. ; 13:3, s. 963-70
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Tidskriftsartikel (refereegranskat)abstract
- Expression of the neuroendocrine marker synaptic vesicle protein 2 (SV2) has been reported in a few cases of gastrointestinal stromal tumors (GISTs). The goal of the present study was to assess the relevance of this finding and identify a possible hormone production in these tumors. We chose to study the orexigen ghrelin and its receptor, since these patients are seldom cachexic, even in advanced disease stages. We investigated ghrelin expression by means of immunohistochemistry on frozen or paraffin-embedded sections from 22 GISTs from a well-characterized patient material. Expression of the growth hormone secretagogue receptor, the ghrelin receptor, was investigated in a subset of lesions. In six tumors, mRNA levels of ghrelin, the ghrelin receptor, and SV2 were analyzed by real-time quantitative PCR. Totally 17 out of 22 tumors showed immunoreactivity for ghrelin. Five out of ten tumors were immunoreactive for the ghrelin receptor, and all of these co-expressed ghrelin. All tumors expressed ghrelin, ghrelin receptor, and SV2 mRNA. GISTs frequently express SV2, ghrelin, and its receptor, indicating the presence of autocrine/paracrine loops.
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| 2. |
- Granberg, Dan, et al.
(författare)
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Gastrin-releasing-peptide in neuroendorine tumours
- 2006
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:1, s. 23-27
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Tidskriftsartikel (refereegranskat)abstract
- In a substantial proportion of cases with endocrine malignant disease the primary lesion cannot be localised and the pathologist hesitates upon the origin of the tumour. Well differentiated neuroendocrine carcinomas of the small bowel can usually be identified by the strong serotonin immunoreactivity, but foregut carcinoids may also stain positive for serotonin and the differential diagnosis between the various foregut tumours may be difficult. We examined if immunostaining for gastrin-releasing-peptide (GRP) may aid in establishing the origin of an unknown neuroendocrine tumour. Tumour tissue from 79 patients (27 lung carcinoids, 4 thymic carcinoids, 4 gastric neuroendocrine tumours, 17 pancreatic well differentiated neuroendocrine carcinomas, 1 duodenal well differentiated neuroendocrine tumour and 26 well differentiated neuroendocrine carcinomas of the small bowel) were immunostained with antibodies against GRP and serotonin. Positive staining for GRP was found in 12/27 lung carcinoids. All other tumour types were consistently GRP-negative (p?
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| 3. |
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| 4. |
- Jonkers, Y. M. H., et al.
(författare)
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Molecular parameters associated with insulinoma progression : chromosomal instability versus p53 and CK19 status
- 2006
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Ingår i: Cytogenetic and Genome Research. - : S. Karger AG. - 1424-8581 .- 1424-859X. ; 115:3-4, s. 289-297
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Tidskriftsartikel (refereegranskat)abstract
- Insulinomas represent the predominant syndromic subtype of endocrine pancreatic tumors (EPTs). Their metastatic potential cannot be predicted reliably using histopathological criteria. In the past few years, several attempts have been made to identify prognostic markers, among them TP53 mutations and immunostaining of p53 and recently cytokeratin 19 (CK19). In a previous study using conventional comparative genomic hybridization (CGH) we have shown that chromosomal instability (CIN) is associated with metastatic disease in insulinomas. It was our aim to evaluate these potential parameters in a single study. For the determination of CIN, we applied CGH to microarrays because it allows a high-resolution detection of DNA copy number changes in comparison with conventional CGH as well as the analysis of chromosomal regions close to the centromeres and telomeres, and at 1pter -> p32, 16p, 19 and 22. These regions are usually excluded from conventional CGH analysis, because they may show DNA gains in negative control hybridizations. Array CGH analysis of 30 insulinomas (15 tumors of benign, eight tumors of uncertain and seven tumors of malignant behavior) revealed that >= 20 chromosomal alterations and >= 6 telomeric losses were the best predictors of malignant progression. A subset of 22 insulinomas was further investigated for TP53 exon 5-8 gene mutations, and p53 and CK19 expression. Only one malignant tumor was shown to harbor an arginine 273 serine mutation and immunopositivity for p53. CK19 immunopositivity was detected in three malignant tumors and one tumor with uncertain behavior. In conclusion, our results indicate that CIN as well as telomeric loss are very powerful indicators for malignant progression in sporadic insulinomas. Our data do not support a critical role for p53 and CK19 as molecular parameters for this purpose.
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| 5. |
- Stålberg, Peter, et al.
(författare)
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Recognizing genes differentially regulated in vitro by the multiple endocrine neoplasia type 1 (MEN1) gene, using RNA interference and oligonucleotide microarrays
- 2006
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Ingår i: Surgery. - : Elsevier BV. - 0039-6060 .- 1532-7361. ; 140:6, s. 921-931
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data on downstream effects of MEN1 gene inactivation is scarce. In an effort to identify genes regulated by MEN1, we designed a silencing experiment in a human endocrine pancreatic tumor cell line (BON1). Methods: By using RNA interference, MEN1 mRNA expression was knocked-down by >85%. Gene expression was assessed by oligonucleotide microarrays and compared to expression in nonsilenced controls. We also investigated if genes were differentially expressed in 6 malignant endocrine pancreatic tumors (EPTs) with homozygous MEN1 inactivation compared to 2 without MEN1 gene alterations. Results: Using a cut-off of ≥2 times, 66 genes were found to be upregulated, and 22 were downregulated in the MEN1-silenced clones. We corroborated the microarray findings by performing quantitative-PCR on the RNA from the silencing experiments for 7 of the 88 differentially regulated genes. Genes involved in endocrine cell fate determination, as well as genes known to be involved in NFkappaB, Notch, and Wnt signaling pathways, were among genes verified as differentially regulated in vitro. Conclusions: The demonstration of pathways affected by silencing of MEN1 in vitro provides novel insight into neoplastic processes of potential importance in vivo, which warrants further study.
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