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

Previous studies of molecular prognostic markers following resection for ex ocrine 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 wit h standard pathological prognostic variables. Formalin-fixed, paraffin-embe dded specimens of pancreatic ductal adenocarcinoma were analysed from 157 p atients [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([NK4) p53, p2[(WAF1), cyclin DI, erbB-2 and erbB-3. Muta tions in codons 12 and 13 of the K-ros oncogene were detected by SSCP and s equencing following DNA extraction and amplification by PCR. The median (ra nge) survival post-resection was 12.5 (3-83) months. Abnormalities of pl6([ NK4), p53, p21(WAF1), cyclin DI, erbB-2 and erbB-3 expression were found in 87%, 41%, 75%, 72%, 33% and 57% of cases, respectively. There was no signi ficant correlation between expression of any of these markers and patient s urvival. K-ras mutations were found in 73 (75%) of 97 cases with amplifiabl e 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 wit h GaT, cGT and GcT K-ras mutations compared to GtT, aGT and GaC mutations. In conclusion, survival was associated with type of K-ros mutation but not expression of p16(INK4), p53, p21(WAFI), cyclin DI, erbB-2 and erbB-3. Int. J. Cancer (Pred. Oncol.) 89: 469-474, 2000. (C) 2000 Wiley-Liss, Inc.