Translational Research in Pancreatic Cancer

169: KRAS mutations in a population of patients operated for pancreatic adenocarcinoma [5] Researchers from Denmark presented a translational study on KRAS mutations in early pancreatic cancer. Previous reports had showed that the frequency of KRAS gene mutations in pancreatic cancer was as high as 75-90% [2]. This high percentage of KRAS mutations was representative of all pancreatic cancer stages, which is in fact consisted mainly of stage IV, due to the usual late presentation and diagnosis of these patients. In this study, tumor samples from 277 operated patients for pancreatic adenocarcinoma (n=161) and ampullary cancer (n=116) were tested for KRAS mutations by polymerase chain reaction (PCR) and LightScanner, Idaho Technology Inc., Salt Lake City, UT, USA. For the pancreatic cancer patients group, KRAS was found mutated in 67%, mainly involving codon 12 (57%) and less so codons 13 and 61. Univariate analysis showed that KRAS mutation was associated with short progression free survival (PFS) (hazard ratio (HR): 1.36, 95% confidence interval (CI): 1.01-1.38; P=0.043) and no statistically significant short overall survival (OS) (P=0.10). The authors suggested that the early stage pancreatic cancer group may represent a subpopulation with fewer genetic changes, thus why the lower frequency of KRAS mutations, than the advanced disease group. The prognostic significance of KRAS mutations is rather unclear as the data from literature are conflicting. Abstract #166: Significance of hENT-1 and RRM1 expression in resected pancreatic cancer [6] Apart from their known role in gemcitabine resistance and toxicity, hENT-1 and RRM1 were studied for their potential prognostic value in early resected pancreatic cancer. From 179 patients having undergone pancreaticoduodenectomy for pancreatic adenocarcinoma at the Cleveland Clinic, Ohio, in the United States between 1999 and 2006, RNA was isolated in 84 of them and the expression levels of hENT-1 and RRM1 were evaluated by reverse transcriptasepolymerase chain reaction (RT-PCR). From this cohort of patient, only 18 received adjuvant gemcitabine chemotherapy. Using Cox proportional hazard analysis high hENT-1 levels were associated with better OS (P=0.007) and PFS (P=0.016) compared to low hENT1 expression. The independent prognostic significance of hENT-1 was confirmed on multivariate analysis. As far as RRM1 is concerned, no prognostic value was demonstrated, but patients with low RRM1 levels were likely to benefit from adjuvant gemcitabine. This is consistent with previous studies which had showed that overexpression of RRM1 was associated with poor response to gemcitabine likely due to the increased concentration of nucleotide deoxycytidine triphosphate which is competing the action of gemcitabine.166: Significance of hENT-1 and RRM1 expression in resected pancreatic cancer [6] Apart from their known role in gemcitabine resistance and toxicity, hENT-1 and RRM1 were studied for their potential prognostic value in early resected pancreatic cancer. From 179 patients having undergone pancreaticoduodenectomy for pancreatic adenocarcinoma at the Cleveland Clinic, Ohio, in the United States between 1999 and 2006, RNA was isolated in 84 of them and the expression levels of hENT-1 and RRM1 were evaluated by reverse transcriptasepolymerase chain reaction (RT-PCR). From this cohort of patient, only 18 received adjuvant gemcitabine chemotherapy. Using Cox proportional hazard analysis high hENT-1 levels were associated with better OS (P=0.007) and PFS (P=0.016) compared to low hENT1 expression. The independent prognostic significance of hENT-1 was confirmed on multivariate analysis. As far as RRM1 is concerned, no prognostic value was demonstrated, but patients with low RRM1 levels were likely to benefit from adjuvant gemcitabine. This is consistent with previous studies which had showed that overexpression of RRM1 was associated with poor response to gemcitabine likely due to the increased concentration of nucleotide deoxycytidine triphosphate which is competing the action of gemcitabine. Table 1. Summary of abstracts with translational and pharmacogenomic interest. Abstract Researcher, Institute Title Main findings CommentsResearcher, Institute Title Main findings Comments