K-ras oncogene subtype mutations are associated with survival but not expression of p53, p16 super(INK4A), P21 super(WAF-1), cyclin D1, erbB-2 and erbB-3 in resected pancreatic ductal adenocarcinoma

• Published in: International journal of cancer Vol. 89; no. 6; pp. 469 - 474
• Main Authors: Kawesha, A, Ghaneh, P, Andren-Sandberg, Ae, Oegraed, D, Skar, R, Dawiskiba, S, Evans, J D, Campbell, F, Lemoine, N, Neoptolemos, J P
• Format: Journal Article
• Language: English
• Published: 20.11.2000
• Subjects: cyclin D1; K-ras gene; p16 protein; p21 protein; WAF1 gene
• ISSN: 0020-7136

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 p16 super(INK4), p53, p21 super(WAF1), 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 p16 super(INK4), p53, p21 super(WAF1), 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 p16 super(INK4), p53, p21 super(WAF1), cyclin D1, erbB-2 and erbB-3.