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

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Abstract
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.