| Autor: |
Pavelić, Krešimir, Hrašćan, Reno, Čabrijan, Tomislav, Križanac, Šimun, Eljuga, Damir, Pavelić, Ljubomir, Karapandža, Nikola, Kusić, Zvonimir, Spaventi, Šime, Pavelić, Jasminka |
| Jazyk: |
angličtina |
| Rok vydání: |
1997 |
| Předmět: |
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| Popis: |
Background: The objective of the study was to define the molecular alterations of the tumor suppressor p53 gene that are associated with tumors of the endocrine pancreas: benign and malignant pancreatic insulinomas. Materials and Methods: The expression of the mutant p53 protein was evaluated immunohistochemically on formalin-fixed paraffin-embedded tumor sections (29 benign insulinoma tissues, 9 malignant insulinomas, 2 B-cell hyperplasia specimens, 3 normal pancreatic tissue samples) using monoclonal (Ab-6) antibodies for p53 proteins. Point mutations of the p53 gene were defined by direct sequencing of amplified DNA (asymmetric PCR, exons 4-9) obtained from one B-cell hyperplasia tissue, 5 benign insulinomas and 5 malignant insulinomas. Results: All of the normal pancreatic and B-cell hyperplasia samples as well as most of the benign insulinoma tissues (24 out of 29 samples) were negative for the mutated p53 protein. In malignant insulinomas an overexpression of the p53 protein was found (in 6 out of 9 samples). Point mutation (single base substitution) was detected in two out of five malignant insulinomas. The first tumor harbored a point mutation at codon 151 (CCC->TCC), while the second tumor harbored a mutation at codon 248 (CGG->GGG). Both patients survived 6 and 8 months respectively, after surgery and chemotherapy. No p53 mutations were identified in 5 benign insulinomas and one hyperplasia of the endocrine pancreas. Conclusions: Our results suggest a link between p53 gene alterations and the malignant stage of pancreatic insulinomas. Based upon these results, we have concluded that, in some rare cases, point mutation of the p53 tumor-suppressor gene may play a role in the development of malignant metastatic insulinomas. ŠReferences: 16Ć |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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