OBJECTIVE: Mutations in the KRAS and P53 genes belong to the most frequently observed genetic alterations in pancreatic ductal adenocarcinoma. The aim of this study was to examine the frequency and prognostic impact of KRAS mutations. In addition, we attempted to define molecular subgroups with distinct biologic behavior by combination of KRAS sequencing data with p53 protein expression data. METHODS: KRAS mutational analyses were performed in a study group of 153 patients by Sanger sequencing. Immunohistochemistry for p53 was performed on tissue microarrays. RESULTS: KRAS mutations in codon 12 or 13 were found in 68% of cases. Nuclear staining for p53 was detectable in 110 (68%) of 162 evaluable cases. We found no correlation between KRAS mutational status and p53 expression. KRAS mutational status but not p53 immunohistochemistry was an independent prognostic factor in the study group (P = 0.02). In a stratified analysis according to KRAS mutational status, p53 expression failed to define prognostic groups beyond the impact of KRAS mutational status. CONCLUSIONS: Our results support the crucial role of KRAS mutational status in pancreatic cancer biology. KRAS mutational status may serve as a prognostic marker. However, its predictive role for targeted therapies remains to be evaluated.
OBJECTIVE: Mutations in the KRAS and P53 genes belong to the most frequently observed genetic alterations in pancreatic ductal adenocarcinoma. The aim of this study was to examine the frequency and prognostic impact of KRAS mutations. In addition, we attempted to define molecular subgroups with distinct biologic behavior by combination of KRAS sequencing data with p53 protein expression data. METHODS:KRAS mutational analyses were performed in a study group of 153 patients by Sanger sequencing. Immunohistochemistry for p53 was performed on tissue microarrays. RESULTS:KRAS mutations in codon 12 or 13 were found in 68% of cases. Nuclear staining for p53 was detectable in 110 (68%) of 162 evaluable cases. We found no correlation between KRAS mutational status and p53 expression. KRAS mutational status but not p53 immunohistochemistry was an independent prognostic factor in the study group (P = 0.02). In a stratified analysis according to KRAS mutational status, p53 expression failed to define prognostic groups beyond the impact of KRAS mutational status. CONCLUSIONS: Our results support the crucial role of KRAS mutational status in pancreatic cancer biology. KRAS mutational status may serve as a prognostic marker. However, its predictive role for targeted therapies remains to be evaluated.
Authors: Michael Haas; Steffen Ormanns; Sibylle Baechmann; Anna Remold; Stephan Kruger; Christoph B Westphalen; Jens T Siveke; Patrick Wenzel; Anna Melissa Schlitter; Irene Esposito; Detlef Quietzsch; Michael R Clemens; Erika Kettner; Ruediger P Laubender; Andreas Jung; Thomas Kirchner; Stefan Boeck; Volker Heinemann Journal: Br J Cancer Date: 2017-04-27 Impact factor: 7.640
Authors: Sibylle Baechmann; Steffen Ormanns; Michael Haas; Stephan Kruger; Anna Remold; Dominik Paul Modest; Thomas Kirchner; Andreas Jung; Jens Werner; Volker Heinemann; Stefan Boeck Journal: BMC Cancer Date: 2017-05-26 Impact factor: 4.430