K-ras oncogene subtype mutations are associated with survival but not expression of p53, p16INK4A, p21WAF-1, cyclin D1, erbB-2 and erbB-3 in resected pancreatic ductal adenocarcinoma
| Autor: | Paula Ghaneh, Nicholas R. Lemoine, Sigmund Dawiskiba, Anthony Kawesha, Fiona Campbell, Åke Andrén-Sandberg, John P. Neoptolemos, Dagfinn Ögraed, Robert Skar, James D. Evans |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Cyclin-Dependent Kinase Inhibitor p21 Male Cancer Research Pancreatic disease Receptor ErbB-3 Receptor ErbB-2 medicine.medical_treatment DNA Mutational Analysis Biology medicine.disease_cause Cyclin D1 ErbB Cyclins Proto-Oncogene Proteins Biomarkers Tumor medicine Humans Cyclin-Dependent Kinase Inhibitor p16 Polymorphism Single-Stranded Conformational Aged Mutation Genes erbB Cancer Genes erbB-2 Middle Aged Prognosis medicine.disease Immunohistochemistry Pancreatic Neoplasms Genes ras Oncology Pancreatectomy Cancer research Adenocarcinoma Exocrine pancreatic cancer Female Tumor Suppressor Protein p53 Carrier Proteins Carcinoma Pancreatic Ductal Follow-Up Studies |
| Zdroj: | International Journal of Cancer. 89:469-474 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/1097-0215(20001120)89:6<469::aid-ijc1>3.0.co;2-l |
| Popis: | Previous studies of molecular prognostic markers following resection for exocrine pancreatic cancer have produced conflicting results. Our aim was to undertake a comprehensive analysis of potentially useful molecular markers in a large, multicentre patient population and to compare these markers with standard pathological prognostic variables. Formalin-fixed, paraffin-embedded specimens of pancreatic ductal adenocarcinoma were analysed from 157 patients [100 men and 57 women with a median (range) age of 60 (33–77) years] who had undergone pancreatectomy. Immunohistochemistry was used to detect expression of p16INK4, p53, p21WAF1, cyclin D1, erbB-2 and erbB-3. Mutations in codons 12 and 13 of the K-ras oncogene were detected by SSCP and sequencing following DNA extraction and amplification by PCR. The median (range) survival post-resection was 12.5 (3–83) months. Abnormalities of p16INK4, p53, p21WAF1, cyclin D1, erbB-2 and erbB-3 expression were found in 87%, 41%, 75%, 72%, 33% and 57% of cases, respectively. There was no significant correlation between expression of any of these markers and patient survival. K-ras mutations were found in 73 (75%) of 97 cases with amplifiable DNA. The presence of K-ras mutation alone did not correlate with survival, but there were significant differences in survival according to the type of K-ras mutation (p = 0.0007). Reduced survival was found in patients with GaT, cGT and GcT K-ras mutations compared to GtT, aGT and GaC mutations. In conclusion, survival was associated with type of K-ras mutation but not expression of p16INK4, p53, p21WAF1, cyclin D1, erbB-2 and erbB-3. Int. J. Cancer 89:469–474, 2000. © 2000 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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