Abstract A50: KRAS mutational status and expressions of p53 and S100A4 proteins in pancreatic adenocarcinomas.

Abstract

Introduction: Currently, there are no established molecular predictors of clinical or therapeutic outcome in pancreatic adenocarcinomas. The purpose of this study was to elucidate the relationship between three potential prognostic markers ( KRAS mutations (codons 12 and 13) and S100A4 and p53 protein expression) and differentiation grade and survival in adenocarcinomas of the pancreatobiliary type. S100A4 plays a role in metastatic progression and the TP53 mutations are associated with poor prognosis in many cancers, but their significance as prognostic markers in pancreatic adenocarcinomas are uncertain (1), (2). Pancreatic cancers have a high incidence of activating KRAS mutations but their roles as prognostic factors are not clarified (3). Description: We examined 72 adenocarcinomas of the pancreatobiliary type with origin in the pancreas, stated by light microscopy. The tumors were classified according to the WHO Classification 2010 (4) and graded as: G1 well-differentiated, G2 moderately differentiated, G3 poorly differentiated, and G4 undifferentiated. The tumors were examined for KRAS mutations (codons 12 and 13) and were subjected to semiquantitative evaluation by immunohistochemical (IHC) staining of p53 (p53 (DO-1): sc-126, Santa Cruz Biotechnology, Inc.) (5), and S100A4 (6). KRAS mutational status was obtained by the WE-ARMS method (7). Statistical analyses were performed using SPSS (v.18, Chicago, IL). Results: The well- and middle-differentiated tumors were grouped and we found that 31/39 (.80) had a positive nuclear score for S100A4, 32/39 (.82) had a positive cytoplasm score for S100A4, 30/38 (.79) had a positive score for p53 and 27/30 (.90) were KRAS mutated. The poorly- and undifferentiated tumors were grouped and we found 23/29 (.79) had a positive nuclear score for S100A4, 25/29 (.86) had a positive cytoplasm score for S100A4, 22/29 (.76) had a positive score for p53 and 23/28 (.82) were KRAS mutated. The number of cases analyzed differs from the total number of cases as the quality of the tissue was not adequate for all the analyses in all cases. Conclusions: There are no statistically significant differences between histological grade and IHC score of p53 (nuclear score), S100A4 (nuclear and cytoplasmic score) or KRAS mutational status. Survival analyses will be presented.